Abstract
The seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. One of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (UVR), and its subsequent control of vitamin D production. Here we show how UVR and vitamin D, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne infections. We conducted a thorough comparison of the molecular and cellular mechanisms of action of UVR and vitamin D on pathogen fitness and host immunity and related these to the effects observed in animal models and clinical trials to understand their independent and complementary effects on infectious disease outcome. UVR and vitamin D share common pathways of innate immune activation primarily via antimicrobial peptide production, and adaptive immune suppression. Whilst UVR can induce vitamin D-independent effects in the skin, such as the generation of photoproducts activating interferon signaling, vitamin D has a larger systemic effect due to its autocrine and paracrine modulation of cellular responses in a range of tissues. However, the seasonal patterns in infectious disease prevalence are not solely driven by variation in UVR and vitamin D levels across latitudes. Vector-borne pathogens show a strong seasonality of infection correlated to climatic conditions favoring their replication. Conversely, pathogens, such as influenza A virus, Mycobacterium tuberculosis and human immunodeficiency virus type 1, have strong evidence to support their interaction with vitamin D. Thus, UVR has both vitamin D-dependent and independent effects on infectious diseases; these effects vary depending on the pathogen of interest and the effects can be complementary or antagonistic.
Similar content being viewed by others
Abbreviations
- 1,25(OH)2D:
-
1α,25-Dihydroxy-vitamin D
- 25(OH)D:
-
25-Hydroxy-vitamin D
- 7-DHC:
-
7-Dehydrocholesterol
- AHR:
-
Aryl hydrocarbon receptor
- AMP:
-
Antimicrobial peptide
- APC:
-
Antigen presenting cell
- ARV:
-
Antiretroviral
- BCG:
-
Bacillus Calmette-Guérin
- CPD:
-
Cyclobutane pyrimidine dimers
- dDC:
-
Dermal dendritic cell
- dLN:
-
Draining lymph node
- DC:
-
Dendritic cell
- DTH:
-
Delayed type hypersensitivity
- EBV:
-
Epstein-Barr virus
- ECM:
-
Extracellular matrix
- HIV:
-
Human immunodeficiency virus
- HSV:
-
Herpes simplex virus type 1
- IAV:
-
Influenza A virus
- IL:
-
Interleukin
- LC:
-
Langerhans cells
- LPS:
-
Lipopolysaccharide
- MAPK:
-
Mitogen-activated protein kinases
- MC:
-
Mast Cell
- MDM:
-
Monocyte-derived macrophages
- MN:
-
Monocyte
- mVDR:
-
Membrane vitamin D receptor
- NK:
-
Natural Killer cells
- NO:
-
Nitric oxide
- nVDR:
-
Nuclear vitamin D receptor
- PBMC:
-
Peripheral blood mononuclear cells
- PI3K:
-
Phosphatidylinositol 3-kinase
- PP:
-
Photo products
- PRR:
-
Pattern recognition receptor
- ROS:
-
Reactive oxygen species
- RSV:
-
Respiratory syncytial virus (RSV)
- RTI:
-
Respiratory tract infections
- RXR:
-
Retinoid X receptor
- TB:
-
Tuberculosis
- Th:
-
T helper
- TLR:
-
Toll-like receptors
- Treg:
-
Regulatory T cells
- UCA:
-
trans-Urocanic acid
- UVA:
-
Ultraviolet A radiation
- UVB:
-
Ultraviolet B radiation
- UVR:
-
Ultraviolet radiation
- VDRE:
-
Vitamin D response elements
Notes and references
A. R. Martineau, S. Nhamoyebonde, T. Oni, M. X. Rangaka, S. Marais, N. Bangani, et al., Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa, Proc. Natl. Acad. Sci. U. S. A., 2011, 108, 47 19013–19017
WHO, Using climate to predict disease outbreaks: a review, World Health Organisation, Geneva, 2004.
D. N. Fisman, Seasonality of infectious diseases, Annu. Rev. Public Health, 2007, 28, 127–143
F. B. Mayr, S. Yende and D. C. Angus, Epidemiology of severe sepsis, Virulence, 2014, 5, 1 4–11
N. C. Grassly and C. Fraser, Seasonal infectious disease epidemiology, Proc. Biol. Sci., 2006, 273, 1600 2541–2550
K. A. Murray, N. Preston, T. Allen, C. Zambrana-Torrelio, P. R. Hosseini and P. Daszak, Global biogeography of human infectious diseases, Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 41 12746–12751
V. Guernier, M. E. Hochberg and J. F. Guegan, Ecology drives the worldwide distribution of human diseases, PLoS Biol., 2004, 2, 6 e141
M. Grigalavicius, J. Moan, A. Dahlback and A. Juzeniene, Daily, seasonal, and latitudinal variations in solar ultraviolet A and B radiation in relation to vitamin D production and risk for skin cancer, Int. J. Dermatol., 2016, 55, 1 e23–e28
O. Engelsen, The relationship between ultraviolet radiation exposure and vitamin D status, Nutrients, 2010, 2, 5 482–495
B. Lehmann and M. Meurer, Vitamin D metabolism, Dermatol. Ther., 2010, 23, 1 2–12
A. T. Slominski, Z. Janjetovic, B. E. Fuller, M. A. Zmijewski, R. C. Tuckey, M. N. Nguyen, et al., Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity, PLoS One, 2010, 5, 3 e9907
W. E. Bradshaw and C. M. Holzapfel, Genetic shift in photoperiodic response correlated with global warming, Proc. Natl. Acad. Sci. U. S. A., 2001, 98, 25 14509–14511
E. S. Jensen, S. Lundbye-Christensen, L. Pedersen, H. T. Sorensen and H. C. Schonheyder, Seasonal variation in meningococcal disease in Denmark: relation to age and meningococcal phenotype, Scand. J. Infect. Dis., 2003, 35, 4 226–229
B. Sultan, K. Labadi, J. F. Guegan and S. Janicot, Climate drives the meningitis epidemics onset in west Africa, PLoS Med., 2005, 2, 1 e6
R. R. Colwell, Global climate and infectious disease: the cholera paradigm, Science, 1996, 274, 5295 2025–2031
R. Colwell, P. Epstein, D. Gubler, M. Hall, P. Reiter, J. Shukla, et al., Global climate change and infectious diseases, Emerg. Infect. Dis., 1998, 4, 3 451–452
A. T. Maurelli, A. E. Hromockyj and M. L. Bernardini, Environmental regulation of Shigella virulence, Curr. Top. Microbiol. Immunol., 1992, 180, 95–116
D. A. Ridenour, S. L. Cirillo, S. Feng, M. M. Samrakandi and J. D. Cirillo, Identification of a gene that affects the efficiency of host cell infection by Legionella pneumophila in a temperature-dependent fashion, Infect. Immun., 2003, 71, 11 6256–6263
G. Kapperud, E. Namork and H. J. Skarpeid, Temperature-inducible surface fibrillae associated with the virulence plasmid of Yersinia enterocolitica and Yersinia pseudotuberculosis, Infect. Immun., 1985, 47, 2 561–566
H. Y. Kwon, S. W. Kim, M. H. Choi, A. D. Ogunniyi, J. C. Paton, S. H. Park, et al., Effect of heat shock and mutations in ClpL and ClpP on virulence gene expression in Streptococcus pneumoniae, Infect. Immun., 2003, 71, 7 3757–3765
R. R. Dunn, T. J. Davies, N. C. Harris and M. C. Gavin, Global drivers of human pathogen richness and prevalence, Proc. Biol. Sci., 2010, 277, 1694 2587–2595
S. F. Dowell, Seasonal variation in host susceptibility and cycles of certain infectious diseases, Emerg. Infect. Dis., 2001, 7, 3 369–374
J. J. Cannell, R. Vieth, J. C. Umhau, M. F. Holick, W. B. Grant, S. Madronich, et al., Epidemic influenza and vitamin D, Epidemiol. Infect., 2006, 134, 6 1129–1140
A. Juzeniene, L. W. Ma, M. Kwitniewski, G. A. Polev, Z. Lagunova, A. Dahlback, et al., The seasonality of pandemic and non-pandemic influenzas: the roles of solar radiation and vitamin D, Int. J. Infect. Dis., 2010, 14, 12 e1099–e1105
P. O. Lang and D. Samaras, Aging adults and seasonal influenza: does the vitamin d status (h)arm the body?, J. Aging Res., 2012, 2012, 806198
D. J. Berry, K. Hesketh, C. Power and E. Hypponen, Vitamin D status has a linear association with seasonal infections and lung function in British adults, Br. J. Nutr., 2011, 106, 9 1433–1440
B. A. Cunha, Influenza: historical aspects of epidemics and pandemics, Infect. Dis. Clin. North Am., 2004, 18, 1 141–155
E. Tognotti, Influenza pandemics: a historical retrospect, J. Infect. Dev. Ctries., 2009, 3, 5 331–334
F. T. Chew, S. Doraisingham, A. E. Ling, G. Kumarasinghe and B. W. Lee, Seasonal trends of viral respiratory tract infections in the tropics, Epidemiol. Infect., 1998, 121, 1 121–128
J. J. Cannell, M. Zasloff, C. F. Garland, R. Scragg and E. Giovannucci, On the epidemiology of influenza, Virol. J., 2008, 5, 29
C. K. Li, B. C. Choi and T. W. Wong, Influenza-related deaths and hospitalizations in Hong Kong: a subtropical area, Public Health, 2006, 120, 6 517–524
J. Moan, A. Dahlback, L. Ma and A. Juzeniene, Influenza, solar radiation and vitamin D, Dermatoendocrinology, 2009, 1, 6 307–309
A. S. Shadrin, I. G. Marinich and L. Y. Taros, Experimental and epidemiological estimation of seasonal and climato-geographical features of non-specific resistance of the organism to influenza, J. Hyg., Epidemiol., Microbiol., Immunol., 1977, 21, 2 155–161
M. P. Zykov and A. V. Sosunov, Vaccination activity of live influenza vaccine in different seasons of the year, J. Hyg., Epidemiol., Microbiol., Immunol., 1987, 31, 4 453–459
L. G. Stensballe, J. K. Devasundaram and E. A. Simoes, Respiratory syncytial virus epidemics: the ups and downs of a seasonal virus, Pediatr. Infect. Dis. J., 2003, 22, 2 Suppl S21–S32
M. Koopmans and D. Brown, Seasonality and diversity of Group A rotaviruses in Europe, Acta Paediatr. Suppl., 1999, 88, 426 14–19
Y. Zhou, L. Li, B. Kim, K. Kaneshi, S. Nishimura, T. Kuroiwa, et al., Rotavirus infection in children in Japan, Pediatr. Int., 2000, 42, 4 428–439
S. M. Cook, R. I. Glass, C. W. LeBaron and M. S. Ho, Global seasonality of rotavirus infections, Bull. World Health Organ., 1990, 68, 2 171–177
F. Termorshuizen, R. B. Geskus, M. T. Roos, R. A. Coutinho, H. Van Loveren, Seasonal influences on immunological parameters in HIV-infected homosexual men: searching for the immunomodulating effects of sunlight, Int. J. Hyg. Environ. Health, 2002, 205, 5 379–384
J. H. Maclachlan, C. J. Lavender and B. C. Cowie, Effect of latitude on seasonality of tuberculosis, Australia, 2002–2011, Emerg. Infect. Dis., 2012, 18, 11 1879–1881
L. E. Thorpe, T. R. Frieden, K. F. Laserson, C. Wells and G. R. Khatri, Seasonality of tuberculosis in India: is it real and what does it tell us?, Lancet, 2004, 364, 9445 1613–1614
M. D. Willis, C. A. Winston, C. M. Heilig, K. P. Cain, N. D. Walter, W. R. Mac Kenzie, Seasonality of tuberculosis in the United States, 1993–2008, Clin. Infect. Dis., 2012, 54, 11 1553–1560
R. J. Wilkinson, M. Llewelyn, Z. Toossi, P. Patel, G. Pasvol, A. Lalvani, et al., Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study, Lancet, 2000, 355, 9204 618–621
N. Talat, S. Perry, J. Parsonnet, G. Dawood and R. Hussain, Vitamin D deficiency and tuberculosis progression, Emerg. Infect. Dis., 2010, 16, 5 853–855
A. Fares, Seasonality of tuberculosis, J. Global Infect. Dis., 2011, 3, 1 46–55
A. M. Molesworth, M. C. Thomson, S. J. Connor, M. P. Cresswell, A. P. Morse, P. Shears, et al., Where is the meningitis belt? Defining an area at risk of epidemic meningitis in Africa, Trans. R. Soc. Trop. Med. Hyg., 2002, 96, 3 242–249
A. J. Pollard and D. Scheifele, Meningococcal disease and vaccination in North America, J. Paediatr. Child Health, 2001, 37, 5 S20–S27
M. Emch, C. Feldacker, M. S. Islam and M. Ali, Seasonality of cholera from 1974 to 2005: a review of global patterns, Int. J. Health Geogr., 2008, 7, 31
W. Checkley, L. D. Epstein, R. H. Gilman, D. Figueroa, R. I. Cama, J. A. Patz, et al., Effect of El Nino and ambient temperature on hospital admissions for diarrhoeal diseases in Peruvian children, Lancet, 2000, 355, 9202 442–450
M. S. Islam, B. S. Drasar and R. B. Sack, The aquatic flora and fauna as reservoirs of Vibrio cholerae: a review, J. Diarrhoeal. Dis. Res., 1994, 12, 2 87–96
P. Siriyasatien, A. Phumee, P. Ongruk, K. Jampachaisri and K. Kesorn, Analysis of significant factors for dengue fever incidence prediction, BMC Bioinformatics, 2016, 17, 166
E. Odongo-Aginya, G. Ssegwanyi, P. Kategere and P. C. Vuzi, Relationship between malaria infection intensity and rainfall pattern in Entebbe peninsula, Uganda, Afr. Health Sci., 2005, 5, 3 238–245
G. C. Ejezie and E. N. Ezedinachi, Malaria parasite density and body temperature in children under 10 years of age in Calabar, Nigeria, Trop. Geogr. Med., 1992, 44, 1–2 97–101
P. Bouvier, A. Rougemont, N. Breslow, O. Doumbo, V. Delley, A. Dicko, et al., Seasonality and malaria in a west African village: does high parasite density predict fever incidence?, Am. J. Epidemiol., 1997, 145, 9 850–857
X. He, J. Yan, X. Zhu, Q. Wang, W. Pang, Z. Qi, et al., Vitamin D inhibits the occurrence of experimental cerebral malaria in mice by suppressing the host inflammatory response, J. Immunol., 2014, 193, 3 1314–1323
K. V. Luong and L. T. Nguyen, The role of vitamin D in malaria, J. Infect. Dev. Ctries., 2015, 9, 1 8–19
S. E. Cusick, R. O. Opoka, T. C. Lund, C. C. John and L. E. Polgreen, Vitamin D insufficiency is common in Ugandan children and is associated with severe malaria, PLoS One, 2014, 9, 12 e113185
A.-L. Khoo, H. J. P. M. Koenen, L. Y. A. Chai, F. C. G. J. Sweep, M. G. Netea, A. J. A. M. van der Ven, et al., Seasonal variation in vitamin D3 levels is paralleled by changes in the peripheral blood human T cell compartment, PLoS One, 2012, 7, 1 e29250
A. L. Khoo, L. Y. Chai, H. J. Koenen, F. C. Sweep, I. Joosten, M. G. Netea, et al., Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals, Clin. Exp. Immunol., 2011, 164, 1 72–79
A. K. Coussens, C. E. Naude, R. Goliath, G. Chaplin, R. J. Wilkinson and N. G. Jablonski, High-dose vitamin D3 reduces deficiency caused by low UVB exposure and limits HIV-1 replication in urban Southern Africans, Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 26 8052–8057
X. C. Dopico, M. Evangelou, R. C. Ferreira, H. Guo, M. L. Pekalski, D. J. Smyth, et al., Widespread seasonal gene expression reveals annual differences in human immunity and physiology, Nat. Commun., 2015, 6, 7000
T. J. John and P. Jayabal, Oral polio vaccination of children in the tropics. I. The poor seroconversion rates and the absence of viral interference, Am. J. Epidemiol., 1972, 96, 4 263–269
G. A. Colditz, T. F. Brewer, C. S. Berkey, M. E. Wilson, E. Burdick, H. V. Fineberg, et al., Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature, J. Am. Med. Assoc., 1994, 271, 9 698–702
T. A. Swartz, P. Skalska, C. G. Gerichter and W. C. Cockburn, Routine administration of oral polio vaccine in a subtropical area. Factors possibly influencing sero-conversion rates, J. Hyg., 1972, 70, 4 719–726
F. Termorshuizen, J. Garssen, M. Norval, L. Koulu, J. Laihia, L. Leino, et al., A review of studies on the effects of ultraviolet irradiation on the resistance to infections: evidence from rodent infection models and verification by experimental and observational human studies, Int. Immunopharmacol., 2002, 2, 2–3 263–275
N. Linder, Y. Abudi, W. Abdalla, M. Badir, Y. Amitai, J. Samuels, et al., Effect of season of inoculation on immune response to rubella vaccine in children, J. Trop. Pediatr., 2011, 57, 4 299–302
L. J. Rothschild, The influence of UV radiation on protistan evolution, J. Eukaryot. Microbiol., 1999, 46, 5 548–555
S. D. Keil, P. Kiser, J. J. Sullivan, A. S. Kong, H. L. Reddy, A. Avery, et al., Inactivation of Plasmodium spp. in plasma and platelet concentrates using riboflavin and ultraviolet light, Transfusion, 2013, 53, 10 2278–2286
L. J. Cardo, F. J. Rentas, L. Ketchum, J. Salata, R. Harman, W. Melvin, et al., Pathogen inactivation of Leishmania donovani infantum in plasma and platelet concentrates using riboflavin and ultraviolet light, Vox Sang., 2006, 90, 2 85–91
A. P. Cap, H. F. Pidcoke, S. D. Keil, H. M. Staples, M. Anantpadma, R. Carrion Jr., et al., Treatment of blood with a pathogen reduction technology using ultraviolet light and riboflavin inactivates Ebola virus in vitro, Transfusion, 2016, 56, Suppl 1 S6–15
J. R. Wikler, N. Janssen, D. P. Bruynzeel and C. Nieboer, The effect of UV-light on pityrosporum yeasts: ultrastructural changes and inhibition of growth, Acta Derm. Venereol., 1990, 70, 1 69–71
S. H. Silva, A. C. Guedes, B. Gontijo, A. M. Ramos, L. S. Carmo, L. M. Farias, et al., Influence of narrow-band UVB phototherapy on cutaneous microbiota of children with atopic dermatitis, J. Eur. Acad. Dermatol. Venereol., 2006, 20, 9 1114–1120
R. W. Truman and T. P. Gillis, The effect of ultraviolet light radiation on Mycobacterium leprae, Int. J. Lepr. Other Mycobact. Dis., 2000, 68, 1 11–17
H. L. David, W. D. Jones Jr. and C. M. Newman, Ultraviolet light inactivation and photoreactivation in the mycobacteria, Infect. Immun., 1971, 4, 3 318–319
B. Zeina, J. Greenman, W. M. Purcell and B. Das, Killing of cutaneous microbial species by photodynamic therapy, Br. J. Dermatol., 2001, 144, 2 274–278
V. Patra, S. N. Byrne and P. Wolf, The Skin Microbiome: Is It Affected by UV-induced Immune Suppression?, Front. Microbiol., 2016, 7, 1235
S. E. Ullrich, Mechanisms underlying UV-induced immune suppression, Mutat Res., 2005, 571, 1–2 185–205
M. Norval, P. McLoone, A. Lesiak and J. Narbutt, The effect of chronic ultraviolet radiation on the human immune system, Photochem. Photobiol., 2008, 84, 1 19–28
B. E. Clausen and J. M. Kel, Langerhans cells: critical regulators of skin immunity?, Immunol. Cell Biol., 2010, 88, 4 351–360
G. G. Krueger and G. Stingl, Immunology/inflammation of the skin–a 50-year perspective, J. Invest. Dermatol., 1989, 92, 4 Suppl 32S–51S
P. S. Friedmann, I. Strickland, A. A. Memon and P. M. Johnson, Early time course of recruitment of immune surveillance in human skin after chemical provocation, Clin. Exp. Immunol., 1993, 91, 3 351–356
F. O. Nestle, P. Di Meglio, J. Z. Qin and B. J. Nickoloff, Skin immune sentinels in health and disease, Nat. Rev. Immunol., 2009, 9, 10 679–691
E. C. De Fabo and F. P. Noonan, Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology, J. Exp. Med., 1983, 158, 1 84–98
R. L. Gallo and J. J. Bernard, Innate immune sensors stimulate inflammatory and immunosuppressive responses to UVB radiation, J. Invest. Dermatol., 2014, 134, 6 1508–1511
G. M. Halliday, S. N. Byrne, J. M. Kuchel, T. S. Poon and R. S. Barnetson, The suppression of immunity by ultraviolet radiation: UVA, nitric oxide and DNA damage, Photochem. Photobiol. Sci., 2004, 3, 8 736–740
P. H. Hart, S. Gorman, J. J. Finlay-Jones, Modulation of the immune system by UV radiation: more than just the effects of vitamin D?, Nat. Rev. Immunol., 2011, 11, 9 584–596
M. P. Stapelberg, R. B. Williams, S. N. Byrne and G. M. Halliday, The alternative complement pathway seems to be a UVA sensor that leads to systemic immunosuppression, J. Invest. Dermatol., 2009, 129, 11 2694–2701
P. J. Rochette, J. P. Therrien, R. Drouin, D. Perdiz, N. Bastien, E. A. Drobetsky, et al., UVA-induced cyclobutane pyrimidine dimers form predominantly at thymine-thymine dipyrimidines and correlate with the mutation spectrum in rodent cells, Nucleic Acids Res., 2003, 31, 11 2786–2794
M. G. Kemp, L. A. Lindsey-Boltz and A. Sancar, UV Light Potentiates STING (Stimulator of Interferon Genes)-dependent Innate Immune Signaling through Deregulation of ULK1 (Unc51-like Kinase 1), J. Biol. Chem., 2015, 290, 19 12184–12194
C. Esser, I. Bargen, H. Weighardt, T. Haarmann-Stemmann and J. Krutmann, Functions of the aryl hydrocarbon receptor in the skin, Semin. Immunopathol., 2013, 35, 6 677–691
Y. Xiang, G. Liu, L. Yang and J. L. Zhong, UVA-induced protection of skin through the induction of heme oxygenase-1, BioSci. Trends, 2011, 5, 6 239–244
L. Feldmeyer, M. Keller, G. Niklaus, D. Hohl, S. Werner and H. D. Beer, The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes, Curr. Biol., 2007, 17, 13 1140–1145
T. H. Nasti and L. Timares, Inflammasome activation of IL-1 family mediators in response to cutaneous photodamage, Photochem. Photobiol., 2012, 88, 5 1111–1125
J. Jans, G. A. Garinis, W. Schul, A. van Oudenaren, M. Moorhouse, M. Smid, et al., Differential role of basal keratinocytes in UV-induced immunosuppression and skin cancer, Mol. Cell. Biol., 2006, 26, 22 8515–8526
G. Soong, J. Chun, D. Parker and A. Prince, Staphylococcus aureus activation of caspase 1/calpain signaling mediates invasion through human keratinocytes, J. Infect. Dis., 2012, 205, 10 1571–1579
K. Kitur, S. Wachtel, A. Brown, M. Wickersham, F. Paulino, H. F. Penaloza, et al., Necroptosis Promotes Staphylococcus aureus Clearance by Inhibiting Excessive Inflammatory Signaling, Cell Rep., 2016, 16, 8 2219–2230
Y. He, R. Fisher, S. Chowdhury, I. Sultana, C. P. Pereira, M. Bray, et al., Vaccinia virus induces rapid necrosis in keratinocytes by a STAT3-dependent mechanism, PLoS One, 2014, 9, 11 e113690
J. Schauber and R. L. Gallo, Antimicrobial peptides and the skin immune defense system, J. Allergy Clin. Immunol., 2009, 124, 3 Suppl 2 R13–R18
M. Frohm, B. Agerberth, G. Ahangari, M. Stahle-Backdahl, S. Liden, H. Wigzell, et al., The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders, J. Biol. Chem., 1997, 272, 24 15258–15263
R. A. Dorschner, V. K. Pestonjamasp, S. Tamakuwala, T. Ohtake, J. Rudisill, V. Nizet, et al., Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus, J. Invest. Dermatol., 2001, 117, 1 91–97
S. P. Hong, M. J. Kim, M. Y. Jung, H. Jeon, J. Goo, S. K. Ahn, et al., Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement, J. Invest. Dermatol., 2008, 128, 12 2880–2887
R. Glaser, F. Navid, W. Schuller, C. Jantschitsch, J. Harder, J. M. Schroder, et al., UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo, J. Allergy Clin. Immunol., 2009, 123, 5 1117–1123
F. Navid, M. Boniotto, C. Walker, K. Ahrens, E. Proksch, T. Sparwasser, et al., Induction of regulatory T cells by a murine beta-defensin, J. Immunol., 2012, 188, 2 735–743
T. Schwarz, The Many Faces of UVR-Induced Immunosuppression, J. Investig. Dermatol. Symp. Proc., 2015, 17, 1 22–23
J. Yu, N. Mookherjee, K. Wee, D. M. Bowdish, J. Pistolic, Y. Li, et al., Host defense peptide LL-37, in synergy with inflammatory mediator IL-1beta, augments immune responses by multiple pathways, J. Immunol., 2007, 179, 11 7684–7691
S. Salzer, S. Kresse, Y. Hirai, S. Koglin, M. Reinholz, T. Ruzicka, et al., Cathelicidin peptide LL-37 increases UVB-triggered inflammasome activation: possible implications for rosacea, J. Dermatol. Sci., 2014, 76, 3 173–179
N. K. Gibbs and M. Norval, Photoimmunosuppression: a brief overview, Photodermatol., Photoimmunol. Photomed., 2013, 29, 2 57–64
E. Damiani and S. E. Ullrich, Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer, Prog. Lipid Res., 2016, 63, 14–27
A. Sleijffers, J. Garssen, H. Van Loveren, Ultraviolet radiation, resistance to infectious diseases, and vaccination responses, Methods, 2002, 28, 1 111–121
A. Jeevan, R. Evans, E. L. Brown and M. L. Kripke, Effect of local ultraviolet irradiation on infections of mice with Candida albicans, Mycobacterium bovis BCG, and Schistosoma mansoni, J. Invest. Dermatol., 1992, 99, 1 59–64
A. Jeevan, S. E. Ullrich, M. De Gracia, R. Shah and Y. Sun, Mechanism of UVB-induced suppression of the immune response to Mycobacterium bovis bacillus Calmette-Guerin: role of cytokines on macrophage function, Photochem. Photobiol., 1996, 64, 2 259–266
A. Jeevan, K. Gilliam, H. Heard and M. L. Kripke, Effects of ultraviolet radiation on the pathogenesis of Mycobacterium lepraemurium infection in mice, Exp. Dermatol., 1992, 1, 3 152–160
J. Garssen, M. Norval, J. Crosby, P. Dortant, H. Van Loveren, The role of urocanic acid in UVB-induced suppression of immunity to Trichinella spiralis infection in the rat, Immunology, 1999, 96, 2 298–306
W. Goettsch, J. Garssen, A. de Klerk, T. M. Herremans, P. Dortant, F. R. de Gruijl, et al. Effects of ultraviolet-B exposure on the resistance to Listeria monocytogenes in the rat, Photochem. Photobiol., 1996, 63, 5 672–679
J. Garssen, H. Van der Vliet, A. De Klerk, W. Goettsch, J. A. Dormans, C. A. Bruggeman, et al., A rat cytomegalovirus infection model as a tool for immunotoxicity testing, Eur. J. Pharmacol., 1995, 292, 3–4 223–231
K. Yamamoto, R. Ito, M. Koura and T. Kamiyama, UV-B irradiation increases susceptibility of mice to malarial infection, Infect. Immun., 2000, 68, 4 2353–2355
Y. M. Denkins and M. L. Kripke, Effect of UV irradiation on lethal infection of mice with Candida albicans, Photochem. Photobiol., 1993, 57, 2 266–271
J. W. Gilmour and M. Norval, The effect of ultraviolet B irradiation, cis-urocanic acid and tumour necrosis factor-alpha on delayed hypersensitivity to herpes simplex virus, Photodermatol., Photoimmunol. Photomed., 1992, 9, 6 255–261
A. A. El-Ghorr, G. Horsburgh and M. Norval, The effect of UVB irradiation on antibody responses during herpes simplex virus type 1 (HSV-1) infections of mice, Photodermatol., Photoimmunol. Photomed., 1998, 14, 1 17–25
L. K. Ryan, D. L. Neldon, L. R. Bishop, M. I. Gilmour, M. J. Daniels and D. M. Sailstad, et al. Exposure to ultraviolet radiation enhances mortality and pathology associated with influenza virus infection in mice, Photochem. Photobiol., 2000, 72, 4 497–507
E. L. Brown, S. E. Ullrich, M. Pride and M. L. Kripke, The effect of UV irradiation on infection of mice with Borrelia burgdorferi, Photochem. Photobiol., 2001, 73, 5 537–544
S. H. Giannini, Effects of ultraviolet B irradiation on cutaneous leishmaniasis, Parasitol. Today, 1992, 8, 2 44–48
M. D. Ward, D. M. Sailstad, D. L. Andrews, E. H. Boykin and M. K. Selgrade, Ultraviolet radiation downregulates allergy in BALB/c mice, J. Toxicol. Environ. Health, Part A, 2004, 67, 1 73–85
N. L. Letvin, R. S. Kauffman and R. Finberg, T lymphocyte immunity to reovirus: cellular requirements for generation and role in clearance of primary infections, J. Immunol., 1981, 127, 6 2334–2339
C. M. Brozek, G. M. Shopp, S. L. Ryan, P. M. Gillespie, D. F. Kusewitt, M. S. Rajagopalan, et al., In vivo exposure to ultraviolet radiation enhances pathogenic effects of murine leukemia virus, LP-BM5, in murine acquired immunodeficiency syndrome, Photochem. Photobiol., 1992, 56, 3 287–295
F. P. Noonan and F. A. Lewis, UVB-induced immune suppression and infection with Schistosoma mansoni, Photochem. Photobiol., 1995, 61, 1 99–105
M. Norval and G. M. Halliday, The consequences of UV-induced immunosuppression for human health, Photochem. Photobiol., 2011, 87, 5 965–977
M. Ichihashi, H. Nagai and K. Matsunaga, Sunlight is an important causative factor of recurrent herpes simplex, Cutis, 2004, 74, 5 Suppl 14–18
D. D. Moyal and A. M. Fourtanier, Broad-spectrum sunscreens provide better protection from solar ultraviolet-simulated radiation and natural sunlight-induced immunosuppression in human beings, J. Am. Acad. Dermatol., 2008, 58, 5 Suppl 2 S149–S154
B. Guo, S. Naish, W. Hu and S. Tong, The potential impact of climate change and ultraviolet radiation on vaccine-preventable infectious diseases and immunization service delivery system, Expert Rev. Vaccines, 2015, 14, 4 561–577
M. K. Sharma, V. Bhatia and H. M. Swami, Outbreak of measles amongst vaccinated children in a slum of Chandigarh, Indian J. Med. Sci., 2004, 58, 2 47–53
S. A. Snopov, S. M. Kharit, M. Norval and V. V. Ivanova, Circulating leukocyte and cytokine responses to measles and poliovirus vaccination in children after ultraviolet radiation exposures, Arch. Virol., 2005, 150, 9 1729–1743
A. Sleijffers, B. Yucesoy, M. Kashon, J. Garssen, F. R. De Gruijl, G. J. Boland, et al., Cytokine polymorphisms play a role in susceptibility to ultraviolet B-induced modulation of immune responses after hepatitis B vaccination, J. Immunol., 2003, 170, 6 3423–3428
A. Sleijffers, A. Kammeyer, F. R. de Gruijl, G. J. Boland, J. van Hattum, W. A. van Vloten, et al., Epidermal cis-urocanic acid levels correlate with lower specific cellular immune responses after hepatitis B vaccination of ultraviolet B-exposed humans, Photochem. Photobiol., 2003, 77, 3 271–275
M. C. Naranjo, J. M. Guerrero, A. Rubio, P. J. Lardone, A. Carrillo-Vico, M. P. Carrascosa-Salmoral, et al., Melatonin biosynthesis in the thymus of humans and rats, Cell. Mol. Life Sci., 2007, 64, 6 781–790
A. Carrillo-Vico, J. R. Calvo, P. Abreu, P. J. Lardone, S. Garcia-Maurino, R. J. Reiter, et al., Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance, FASEB J., 2004, 18, 3 537–539
V. Srinivasan, D. W. Spence, I. Trakht, S. R. Pandi-Perumal, D. P. Cardinali and G. J. Maestroni, Immunomodulation by melatonin: its significance for seasonally occurring diseases, Neuroimmunomodulation, 2008, 15, 2 93–101
R. Hardeland, Melatonin in aging and disease -multiple consequences of reduced secretion, options and limits of treatment, Aging Dis., 2012, 3, 2 194–225
K. Honma, S. Honma, M. Kohsaka and N. Fukuda, Seasonal variation in the human circadian rhythm: dissociation between sleep and temperature rhythm, Am. J. Physiol., 1992, 262, 5 Pt 2 R885–R891
T. Ueno-Towatari, K. Norimatsu, K. Blazejczyk, H. Tokura and T. Morita, Seasonal variations of melatonin secretion in young females under natural and artificial light conditions in Fukuoka, Japan, J. Physiol. Anthropol., 2007, 26, 2 209–215
T. W. Fischer, T. W. Sweatman, I. Semak, R. M. Sayre, J. Wortsman and A. Slominski, Constitutive and UV-induced metabolism of melatonin in keratinocytes and cell-free systems, FASEB J., 2006, 20, 9 1564–1566
M. J. Barjavel, Z. Mamdouh, N. Raghbate and O. Bakouche, Differential expression of the melatonin receptor in human monocytes, J. Immunol., 1998, 160, 3 1191–1197
M. A. Lopez-Gonzalez, J. R. Calvo, J. J. Segura and J. M. Guerrero, Characterization of melatonin binding sites in human peripheral blood neutrophils, Biotechnol. Ther., 1993, 4, 3–4 253–262
D. L. Drazen and R. J. Nelson, Melatonin receptor subtype MT2 (Mel 1b) and not mt1 (Mel 1a) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity, Neuroendocrinology, 2001, 74, 3 178–184
A. Carrillo-Vico, R. J. Reiter, P. J. Lardone, J. L. Herrera, R. Fernandez-Montesinos, J. M. Guerrero, et al., The modulatory role of melatonin on immune responsiveness, Curr. Opin. Investig. Drugs, 2006, 7, 5 423–431
N. E. Waly and R. Hallworth, Circadian Pattern of Melatonin MT1 and MT2 Receptor Localization in the Rat Suprachiasmatic Nucleus, J. Circadian Rhythms, 2015, 13, 1
S. Garcia-Maurino, D. Pozo, J. R. Calvo and J. M. Guerrero, Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines, J. Pineal Res., 2000, 29, 3 129–137
C. Pena, J. Rincon, A. Pedreanez, N. Viera and J. Mosquera, Chemotactic effect of melatonin on leukocytes, J. Pineal Res., 2007, 43, 3 263–269
C. R. Sudfeld, E. L. Giovannucci, S. Isanaka, S. Aboud, F. M. Mugusi, M. Wang, et al., Vitamin D Status and Incidence of Pulmonary Tuberculosis, Opportunistic Infections, and Wasting Among HIV-Infected Tanzanian Adults Initiating Antiretroviral Therapy, J. Infect. Dis., 2013, 207, 3 378–385
J. Charan, J. P. Goyal, D. Saxena and P. Yadav, Vitamin D for prevention of respiratory tract infections: A systematic review and meta-analysis, J. Pharmacol. Pharmacother., 2012, 3, 4 300–303
F. P. Havers, B. Detrick, S. W. Cardoso, S. Berendes, J. R. Lama, P. Sugandhavesa, et al., Change in vitamin d levels occurs early after antiretroviral therapy initiation and depends on treatment regimen in resource-limited settings, PLoS One, 2014, 9, 4 e95164
A. Moodley, M. Qin, K. K. Singh and S. A. Spector, Vitamin D-related host genetic variants alter HIV disease progression in children, Pediatr. Infect. Dis. J., 2013, 32, 11 1230–1236
R. Janssen, L. Bont, C. L. Siezen, H. M. Hodemaekers, M. J. Ermers, G. Doornbos, et al., Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes, J. Infect. Dis., 2007, 196, 6 826–834
A. R. Martineau, A. C. Leandro, S. T. Anderson, S. M. Newton, K. A. Wilkinson, M. P. Nicol, et al., Association between Gc genotype and susceptibility to TB is dependent on vitamin D status, Eur. Respir. J., 2010, 35, 5 1106–1112
R. Bellamy, C. Ruwende, T. Corrah, K. P. McAdam, M. Thursz, H. C. Whittle, et al., Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene, J. Infect. Dis., 1999, 179, 3 721–724
H. Loke, D. Bethell, C. X. Phuong, N. Day, N. White, J. Farrar, et al., Susceptibility to dengue hemorrhagic fever in vietnam: evidence of an association with variation in the vitamin d receptor and Fc gamma receptor IIa genes, Am. J. Trop. Med. Hyg., 2002, 67, 1 102–106
C. R. Sudfeld, E. L. Giovannucci, S. Isanaka, S. Aboud, F. M. Mugusi, M. Wang, et al., Vitamin D status and incidence of pulmonary tuberculosis, opportunistic infections, and wasting among HIV-infected Tanzanian adults initiating antiretroviral therapy, J. Infect. Dis., 2013, 207, 3 378–385
C. R. Sudfeld, M. Wang, S. Aboud, E. L. Giovannucci, F. M. Mugusi and W. W. Fawzi, Vitamin D and HIV progression among Tanzanian adults initiating antiretroviral therapy, PLoS One, 2012, 7, 6 e40036
J. N. Jarvis, T. Bicanic, A. Loyse, G. Meintjes, L. Hogan, C. H. Roberts, et al., Very low levels of 25-hydroxyvitamin D are not associated with immunologic changes or clinical outcome in South African patients with HIV-associated cryptococcal meningitis, Clin. Infect. Dis., 2014, 59, 4 493–500
M. Norval, A. K. Coussens, R. J. Wilkinson, L. Bornman, R. M. Lucas and C. Y. Wright, Vitamin D Status and Its Consequences for Health in South Africa, Int. J. Environ. Res. Public Health, 2016, 13, 10 1019
P. T. Liu, S. Stenger, H. Li, L. Wenzel, B. H. Tan, S. R. Krutzik, et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science, 2006, 311, 5768 1770–1773
M. R. Pinzone, M. Di Rosa, B. M. Celesia, F. Condorelli, M. Malaguarnera, G. Madeddu, et al., LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression leading to vitamin D consumption and hypovitaminosis D in HIV-infected individuals, Eur. Rev. Med. Pharmacol. Sci., 2013, 17, 14 1938–1950
J. E. Smith and D. S. Goodman, The turnover and transport of vitamin D and of a polar metabolite with the properties of 25-hydroxycholecalciferol in human plasma, J. Clin. Invest., 1971, 50, 10 2159–2167
B. S. Levine, F. R. Singer, G. F. Bryce, J. P. Mallon, O. N. Miller and J. W. Coburn, Pharmacokinetics and biologic effects of calcitriol in normal humans, J. Lab. Clin. Med., 1985, 105, 2 239–246
C. A. Coughlan, S. H. Chotirmall, J. Renwick, T. Hassan, T. B. Low, G. Bergsson, et al., The effect of Aspergillus fumigatus infection on vitamin D receptor expression in cystic fibrosis, Am. J. Respir. Crit. Care Med., 2012, 186, 10 999–1007
S. P. Yenamandra, A. Lundin, V. Arulampalam, M. Yurchenko, S. Pettersson, G. Klein, et al., Expression profile of nuclear receptors upon Epstein–Barr virus induced B cell transformation, Exp. Oncol., 2009, 31, 2 92–96
J. T. Go, S. E. Belisle, N. Tchitchek, T. M. Tumpey, W. Ma, J. A. Richt, et al., 2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models, BMC Genomics, 2012, 13, 627
S. Ray, K. S. Kamath, R. Srivastava, D. Raghu, K. Gollapalli, R. Jain, et al., Serum proteome analysis of vivax malaria: An insight into the disease pathogenesis and host immune response, J. Proteomics, 2012, 75, 10 3063–3080
T. T. Wang, L. E. Tavera-Mendoza, D. Laperriere, E. Libby, N. B. MacLeod, Y. Nagai, et al., Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes, Mol. Endocrinol., 2005, 19, 11 2685–2695
A. W. Norman, H. L. Henry, J. E. Bishop, X. D. Song, C. Bula and W. H. Okamura, Different shapes of the steroid hormone 1alpha,25(OH)(2)-vitamin D(3) act as agonists for two different receptors in the vitamin D endocrine system to mediate genomic and rapid responses, Steroids, 2001, 66, 3–5 147–158
S. Alvarez-Diaz, N. Valle, G. Ferrer-Mayorga, L. Lombardia, M. Herrera, O. Dominguez, et al., MicroRNA-22 is induced by vitamin D and contributes to its antiproliferative, antimigratory and gene regulatory effects in colon cancer cells, Hum. Mol. Genet., 2012, 21, 10 2157–2165
S. Chen, G. P. Sims, X. X. Chen, Y. Y. Gu, S. Chen and P. E. Lipsky, Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation, J. Immunol., 2007, 179, 3 1634–1647
J. Fritsche, K. Mondal, A. Ehrnsperger, R. Andreesen and M. Kreutz, Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyvitamin D3 by human dendritic cells, Blood, 2003, 102, 9 3314–3316
H. Sigmundsdottir, J. Pan, G. F. Debes, C. Alt, A. Habtezion, D. Soler, et al., DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27, Nat. Immunol., 2007, 8, 3 285–293
A. M. Ramirez, C. Wongtrakool, T. Welch, A. Steinmeyer, U. Zugel and J. Roman, Vitamin D inhibition of pro-fibrotic effects of transforming growth factor beta1 in lung fibroblasts and epithelial cells, J. Steroid Biochem. Mol. Biol., 2010, 118, 3 142–150
M. Shalita-Chesner, R. Koren, Y. A. Mekori, D. Baram, C. Rotem, U. A. Liberman, et al., 1,25-Dihydroxyvitamin D3 enhances degranulation of mast cells, Mol. Cell. Endocrinol., 1998, 142, 1–2 49–55
E. Gottfried, M. Rehli, J. Hahn, E. Holler, R. Andreesen and M. Kreutz, Monocyte-derived cells express CYP27A1 and convert vitamin D3 into its active metabolite, Biochem. Biophys. Res. Commun., 2006, 349, 1 209–213
L. M. Sly, M. Lopez, W. M. Nauseef and N. E. Reiner, 1alpha,25-Dihydroxyvitamin D3-induced monocyte antimycobacterial activity is regulated by phosphatidylinositol 3-kinase and mediated by the NADPH-dependent phagocyte oxidase, J. Biol. Chem., 2001, 276, 38 35482–35493
K. A. Rockett, R. Brookes, I. Udalova, V. Vidal, A. V. Hill and D. Kwiatkowski, 1,25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line, Infect. Immun., 1998, 66, 11 5314–5321
R. A. Fratti, J. M. Backer, J. Gruenberg, S. Corvera and V. Deretic, Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest, J. Cell Biol., 2001, 154, 3 631–644
A. R. Martineau, K. A. Wilkinson, S. M. Newton, R. A. Floto, A. W. Norman, K. Skolimowska, et al., IFN-gamma- and TNF-Independent Vitamin D-Inducible Human Suppression of Mycobacteria: The Role of Cathelicidin LL-37, J. Immunol., 2007, 178, 11 7190–7198
A. F. Gombart, N. Borregaard and H. P. Koeffler, Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3, FASEB J., 2005, 19, 9 1067–1077
O. E. Sorensen, P. Follin, A. H. Johnsen, J. Calafat, G. S. Tjabringa, P. S. Hiemstra, et al., Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3, Blood, 2001, 97, 12 3951–3959
A. R. Martineau, S. M. Newton, K. A. Wilkinson, B. Kampmann, B. M. Hall, N. Nawroly, et al., Neutrophil-mediated innate immune resistance to mycobacteria, J. Clin. Invest., 2007, 117, 7 1988–1994
G. Diamond, N. Beckloff and L. K. Ryan, Host defense peptides in the oral cavity and the lung: similarities and differences, J. Dent. Res., 2008, 87, 10 915–927
F. Neville, M. Cahuzac, O. Konovalov, Y. Ishitsuka, K. Y. Lee, I. Kuzmenko, et al., Lipid headgroup discrimination by antimicrobial peptide LL-37: insight into mechanism of action, Biophys. J., 2006, 90, 4 1275–1287
C. B. Buck, P. M. Day, C. D. Thompson, J. Lubkowski, W. Lu, D. R. Lowy, et al., Human alpha-defensins block papillomavirus infection, Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 5 1516–1521
M. D. Howell, J. F. Jones, K. O. Kisich, J. E. Streib, R. L. Gallo and D. Y. Leung, Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum, J. Immunol., 2004, 172, 3 1763–1767
P. G. Barlow, P. Svoboda, A. Mackellar, A. A. Nash, I. A. York, J. Pohl, et al., Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37, PLoS One, 2011, 6, 10 e25333
S. M. Currie, E. Gwyer Findlay, A. J. McFarlane, P. M. Fitch, B. Bottcher, N. Colegrave, et al., Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans, J. Immunol., 2016, 196, 6 2699–2710
S. Hansdottir, M. M. Monick, S. L. Hinde, N. Lovan, D. C. Look and G. W. Hunninghake, Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense, J. Immunol., 2008, 181, 10 7090–7099
A. Di Nardo, A. Vitiello and R. L. Gallo, Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide, J. Immunol., 2003, 170, 5 2274–2278
B. Agerberth, J. Charo, J. Werr, B. Olsson, F. Idali, L. Lindbom, et al., The human antimicrobial and chemotactic peptides LL-37 and α-defensins are expressed by specific lymphocyte and monocyte populations, Blood, 2000, 96, 3086–3093
J. M. Yuk, D. M. Shin, H. M. Lee, C. S. Yang, H. S. Jin, K. K. Kim, et al., Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin, Cell Host Microbe, 2009, 6, 3 231–243
P. D. Hart, M. R. Young, A. H. Gordon and K. H. Sullivan, Inhibition of phagosome-lysosome fusion in macrophages by certain mycobacteria can be explained by inhibition of lysosomal movements observed after phagocytosis, J. Exp. Med., 1987, 166, 4 933–946
C. Munz, Enhancing immunity through autophagy, Annu. Rev. Immunol., 2009, 27, 423–449
J. Sun, VDR/vitamin D receptor regulates autophagic activity through ATG16L1, Autophagy, 2016, 12, 6 1057–1058
G. B. Kyei, C. Dinkins, A. S. Davis, E. Roberts, S. B. Singh, C. Dong, et al., Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages, J. Cell Biol., 2009, 186, 2 255–268
G. R. Campbell and S. A. Spector, Hormonally active vitamin D3 (1alpha,25-dihydroxycholecalciferol) triggers autophagy in human macrophages that inhibits HIV-1 infection, J. Biol. Chem., 2011, 286, 21 18890–18902
M. Fabri, S. Stenger, D. M. Shin, J. M. Yuk, P. T. Liu, S. Realegeno, et al., Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages, Sci. Transl. Med., 2011, 3, 104 104ra102
T. T. Wang, B. Dabbas, D. Laperriere, A. J. Bitton, H. Soualhine, L. E. Tavera-Mendoza, et al., Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease, J. Biol. Chem., 2010, 285, 4 2227–2231
P. T. Liu, M. Schenk, V. P. Walker, P. W. Dempsey, M. Kanchanapoomi, M. Wheelwright, et al., Convergence of IL-1beta and VDR activation pathways in human TLR2/1-induced antimicrobial responses, PLoS One, 2009, 4, 6 e5810
S. Kota, A. Sabbah, T. H. Chang, R. Harnack, Y. Xiang, X. Meng, et al., Role of human beta-defensin-2 during tumor necrosis factor-alpha/NF-kappaB-mediated innate antiviral response against human respiratory syncytial virus, J. Biol. Chem., 2008, 283, 33 22417–22429
M. E. Quinones-Mateu, M. M. Lederman, Z. Feng, B. Chakraborty, J. Weber, H. R. Rangel, et al., Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication, AIDS, 2003, 17, 16 F39–F48
Z. Feng, G. R. Dubyak, M. M. Lederman and A. Weinberg, Cutting edge: human beta defensin 3–a novel antagonist of the HIV-1 coreceptor CXCR4, J. Immunol., 2006, 177, 2 782–786
E. Hazrati, B. Galen, W. Lu, W. Wang, Y. Ouyang, M. J. Keller, et al., Human alpha- and beta-defensins block multiple steps in herpes simplex virus infection, J. Immunol., 2006, 177, 12 8658–8666
T. Tecle, M. R. White, D. Gantz, E. C. Crouch and K. L. Hartshorn, Human neutrophil defensins increase neutrophil uptake of influenza A virus and bacteria and modify virus-induced respiratory burst responses, J. Immunol., 2007, 178, 12 8046–8052
S. Ranjbar, L. D. Jasenosky, N. Chow and A. E. Goldfeld, Regulation of Mycobacterium tuberculosis-dependent HIV-1 transcription reveals a new role for NFAT5 in the toll-like receptor pathway, PLoS Pathog., 2012, 8, 4 e1002620
A. A. Giangreco and L. Nonn, The sum of many small changes: microRNAs are specifically and potentially globally altered by vitamin D3 metabolites, J. Steroid Biochem. Mol. Biol., 2013, 136, 86–93
Y. Zhang, D. Y. Leung, B. N. Richers, Y. Liu, L. K. Remigio, D. W. Riches, et al., Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1, J. Immunol., 2012, 188, 5 2127–2135
M. Cohen-Lahav, S. Shany, D. Tobvin, C. Chaimovitz and A. Douvdevani, Vitamin D decreases NFkappaB activity by increasing IkappaBalpha levels, Nephrol. Dial. Transplant., 2006, 21, 4 889–897
S. Hansdottir, M. M. Monick, N. Lovan, L. Powers, A. Gerke and G. W. Hunninghake, Vitamin D decreases respiratory syncytial virus induction of NF-kappaB-linked chemokines and cytokines in airway epithelium while maintaining the antiviral state, J. Immunol., 2010, 184, 2 965–974
A. K. Coussens, R. J. Wilkinson and A. R. Martineau, Phenylbutyrate Is Bacteriostatic against Mycobacterium tuberculosis and Regulates the Macrophage Response to Infection, Synergistically with 25-Hydroxy-Vitamin D3, PLoS Pathog., 2015, 11, 7 e1005007
M. C. Gauzzi, C. Purificato, K. Donato, Y. Jin, L. Wang, K. C. Daniel, et al., Suppressive effect of 1alpha,25-dihydroxyvitamin D3 on type I IFN-mediated monocyte differentiation into dendritic cells: impairment of functional activities and chemotaxis, J. Immunol., 2005, 174, 1 270–276
G. Penna and L. Adorini, 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation, J. Immunol., 2000, 164, 5 2405–2411
A. Giulietti, E. van Etten, L. Overbergh, K. Stoffels, R. Bouillon and C. Mathieu, Monocytes from type 2 diabetic patients have a pro-inflammatory profile. 1,25-Dihydroxyvitamin D(3) works as anti-inflammatory, Diabetes Res. Clin. Pract., 2007, 77, 1 47–57
A. K. Coussens, R. J. Wilkinson, Y. Hanifa, V. Nikolayevskyy, P. T. Elkington, K. Islam, et al., Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment, Proc. Natl. Acad. Sci. U. S. A., 2012, 109, 38 15449–15454
G. Nunnari, P. Fagone, F. Lazzara, A. Longo, D. Cambria, G. Di Stefano, et al., Vitamin D3 inhibits TNFalpha-induced latent HIV reactivation in J-LAT cells, Mol. Cell. Biochem., 2016, 418, 1–2 49–57
D. Boraschi, D. Lucchesi, S. Hainzl, M. Leitner, E. Maier, D. Mangelberger, et al., IL-37: a new anti-inflammatory cytokine of the IL-1 family, Eur. Cytokine Netw., 2011, 22, 3 127–147
M. F. Nold, C. A. Nold-Petry, J. A. Zepp, B. E. Palmer, P. Bufler and C. A. Dinarello, IL-37 is a fundamental inhibitor of innate immunity, Nat. Immunol., 2010, 11, 11 1014–1022
A. W. Pedersen, K. Holmstrom, S. S. Jensen, D. Fuchs, S. Rasmussen, P. Kvistborg, et al., Phenotypic and functional markers for 1alpha,25-dihydroxyvitamin D(3)-modified regulatory dendritic cells, Clin. Exp. Immunol., 2009, 157, 1 48–59
L. Szeles, G. Keresztes, D. Torocsik, Z. Balajthy, L. Krenacs, S. Poliska, et al., 1,25-dihydroxyvitamin D3 is an autonomous regulator of the transcriptional changes leading to a tolerogenic dendritic cell phenotype, J. Immunol., 2009, 182, 4 2074–2083
R. Thien, K. Baier, P. Pietschmann, M. Peterlik and M. Willheim, Interactions of 1 alpha,25-dihydroxyvitamin D3 with IL-12 and IL-4 on cytokine expression of human T lymphocytes, J. Allergy Clin. Immunol., 2005, 116, 3 683–689
J. Smolders, P. Menheere, M. Thewissen, E. Peelen, J. W. Tervaert, R. Hupperts, et al., Regulatory T cell function correlates with serum 25-hydroxyvitamin D, but not with 1,25-dihydroxyvitamin D, parathyroid hormone and calcium levels in patients with relapsing remitting multiple sclerosis, J. Steroid Biochem. Mol. Biol., 2010, 121, 1–2 243–246
A. Coussens, P. M. Timms, B. J. Boucher, T. R. Venton, A. T. Ashcroft, K. H. Skolimowska, et al., 1alpha,25-dihydroxyvitamin D inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection, Immunology, 2009, 127, 4 539–548
P. E. Van den Steen, I. Van Aelst, S. Starckx, K. Maskos, G. Opdenakker and A. Pagenstecher, Matrix metalloproteinases, tissue inhibitors of MMPs and TACE in experimental cerebral malaria, Lab. Invest., 2006, 86, 9 873–888
P. T. Elkington, J. M. D’Armiento and J. S. Friedland, Tuberculosis immunopathology: the neglected role of extracellular matrix destruction, Sci. Transl. Med., 2011, 3, 71 71ps76
J. S. Mort, G. R. Dodge, P. J. Roughley, J. Liu, S. J. Finch, G. DiPasquale, et al., Direct evidence for active metalloproteinases mediating matrix degradation in interleukin 1-stimulated human articular cartilage, Matrix, 1993, 13, 2 95–102
P. Van Lint and C. Libert, Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation, J. Leukoc. Biol., 2007, 82, 6 1375–1381
G. W. Hunninghake, J. M. Davidson, S. Rennard, S. Szapiel, J. E. Gadek and R. G. Crystal, Elastin fragments attract macrophage precursors to diseased sites in pulmonary emphysema, Science, 1981, 212, 4497 925–927
G. S. Tjabringa, J. Aarbiou, D. K. Ninaber, J. W. Drijfhout, O. E. Sorensen, N. Borregaard, et al., The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor, J. Immunol., 2003, 171, 12 6690–6696
d. Yang, Q. Chen, A. P. Schmidt, G. M. Anderson, J. M. Wang, J. Wooters, et al., LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells, J. Exp. Med., 2000, 192, 7 1069–1074
F. Niyonsaba, K. Iwabuchi, H. Matsuda, H. Ogawa and I. Nagaoka, Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway, Int. Immunol., 2002, 14, 4 421–426
D. Yang, Q. Chen, O. Chertov and J. J. Oppenheim, Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells, J. Leukoc. Biol., 2000, 68, 1 9–14
D. Yang, O. Chertov, S. N. Bykovskaia, Q. Chen, M. J. Buffo, J. Shogan, et al., Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6, Science, 1999, 286, 5439 525–528
N. F. Crum-Cianflone, S. Won, R. Lee, T. Lalani, A. Ganesan, T. Burgess, et al., Vitamin D levels and influenza vaccine immunogenicity among HIV-infected and HIV-uninfected adults, Vaccine, 2016, 34, 41 5040–5046
C. Cooper, A. Thorne, G. Canadian Hiv Trials Network Ctn Influenza Vaccine Research, Vitamin D supplementation does not increase immunogenicity of seasonal influenza vaccine in HIV-infected adults, HIV Clin. Trials, 2011, 12, 5 275–276
M. E. Sundaram, H. K. Talbot, Y. Zhu, M. R. Griffin, S. Spencer, D. K. Shay, et al., Vitamin D is not associated with serologic response to influenza vaccine in adults over 50 years old, Vaccine, 2013, 31, 16 2057–2061
M. Science, J. L. Maguire, M. L. Russell, M. Smieja, S. D. Walter and M. Loeb, Serum 25-hydroxyvitamin d level and influenza vaccine immunogenicity in children and adolescents, PLoS One, 2014, 9, 1 e83553
M. K. Lalor, S. Floyd, P. Gorak-Stolinska, R. E. Weir, R. Blitz, K. Branson, et al., BCG vaccination: a role for vitamin D?, PLoS One, 2011, 6, 1 e16709
J. W. Hsu, P. N. Yin, R. Wood, J. Messing, E. Messing and Y. F. Lee, 1 alpha, 25-dihydroxylvitamin D3 promotes Bacillus Calmette-Guerin immunotherapy of bladder cancer, Oncotarget, 2013, 4, 12 2397–2406
M. Green, Cod liver oil and tuberculosis, Br. Med. J., 2011, 343, d7505
H. M. Mackay, H. M. Linford, M. Mitman and M. H. Wild, The therapeutic value of vitamins A and D in measles, Arch. Dis. Child., 1936, 11, 63 127–142
A. R. Martineau, P. M. Timms, G. H. Bothamley, Y. Hanifa, K. Islam, A. P. Claxton, et al., High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial, Lancet, 2011, 377, 9761 242–250
J. Sautet, J. Vuillet and G. Arnaud, [Effects of the immediate adjunction of cod liver oil or vitamin D and calcium biphosphate to antimalarial drugs used in the treatment of Plasmodium berghei infections. II], Bull. Soc. Pathol. Exot. Filiales, 1957, 50, 1 44–49
A. R. Martineau, R. J. Wilkinson, K. A. Wilkinson, S. M. Newton, B. Kampmann, B. M. Hall, et al., A single dose of vitamin D enhances immunity to mycobacteria, Am. J. Respir. Crit. Care Med., 2007, 176, 2 208–213
J. Xia, L. Shi, L. Zhao and F. Xu, Impact of vitamin D supplementation on the outcome of tuberculosis treatment: a systematic review and meta-analysis of randomized controlled trials, Chin. Med. J., 2014, 127, 17 3127–3134
N. Tukvadze, E. Sanikidze, M. Kipiani, G. Hebbar, K. A. Easley, N. Shenvi, et al., High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial, Am. J. Clin. Nutr., 2015, 102, 5 1059–1069
J. Rathored, S. K. Sharma, B. Singh, J. N. Banavaliker, V. Sreenivas, A. K. Srivastava, et al., Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor polymorphisms and serum 25(OH)D, Int. J. Tuberc. Lung Dis., 2012, 16, 11 1522–1528
F. R. Sabin, C. A. Doan and R. S. Cunningham, Studies of the Blood in Experimental Tuberculosis: The Monocyte–Lymphocyte Ratio; the Anemia-Leucopenia Phase, Transactions of the 22nd Annual Meeting of the National Tuberculosis Association, 1926, 22, 252–256
A. K. Coussens, A. R. Martineau and R. J. Wilkinson, Anti-Inflammatory and Antimicrobial Actions of Vitamin D in Combating TB/HIV, Scientifica, 2014, 2014, 903680
A. P. Steenhoff, J. I. Schall, J. Samuel, B. Seme, M. Marape, B. Ratshaa, et al., Vitamin D(3)supplementation in Batswana children and adults with HIV: a pilot double blind randomized controlled trial, PLoS One, 2015, 10, 2 e0117123
L. Coelho, S. W. Cardoso, P. M. Luz, R. M. Hoffman, L. Mendonca, V. G. Veloso, et al., Vitamin D3 supplementation in HIV infection: effectiveness and associations with antiretroviral therapy, Nutr. J., 2015, 14, 81
V. A. Stallings, J. I. Schall, M. L. Hediger, B. S. Zemel, F. Tuluc, K. A. Dougherty, et al., High-dose vitamin D3 supplementation in children and young adults with HIV: a randomized, placebo-controlled trial, Pediatr. Infect. Dis. J., 2015, 34, 2 e32–e40
V. Giacomet, A. Vigano, V. Manfredini, C. Cerini, G. Bedogni, S. Mora, et al., Cholecalciferol supplementation in HIV-infected youth with vitamin D insufficiency: effects on vitamin D status and T-cell phenotype: a randomized controlled trial, HIV Clin. Trials, 2013, 14, 2 51–60
A. Nimer and A. Mouch, Vitamin D improves viral response in hepatitis C genotype 2–3 naive patients, World J. Gastroenterol., 2012, 18, 8 800–805
M. Atsukawa, A. Tsubota, N. Shimada, K. Yoshizawa, H. Abe, T. Asano, et al., Effect of native vitamin D3 supplementation on refractory chronic hepatitis C patients in simeprevir with pegylated interferon/ribavirin, Hepatol. Res., 2016, 46, 5 450–458
E. Falleti, D. Bitetto, C. Fabris, G. Fattovich, A. Cussigh, S. Cmet, et al., Vitamin D binding protein gene polymorphisms and baseline vitamin D levels as predictors of antiviral response in chronic hepatitis C, Hepatology, 2012, 56, 5 1641–1650
E. Rosjo, A. Lossius, N. Abdelmagid, J. C. Lindstrom, M. T. Kampman, L. Jorgensen, et al., Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis, Mult. Scler., 2016, 10.1177/1352458516654310
A. Najafipoor, R. Roghanian, S. H. Zarkesh-Esfahani, M. Bouzari and M. Etemadifar, The beneficial effects of vitamin D3 on reducing antibody titers against Epstein-Barr virus in multiple sclerosis patients, Cell. Immunol., 2015, 294, 1 9–12
P. Bergman, A. U. Lindh, L. Bjorkhem-Bergman and J. D. Lindh, Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, PLoS One, 2013, 8, 6 e65835
D. A. Jolliffe, C. J. Griffiths and A. R. Martineau, Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies, J. Steroid Biochem. Mol. Biol., 2013, 136, 321–329
A. E. Reeme and R. T. Robinson, Dietary Vitamin D3 Suppresses Pulmonary Immunopathology Associated with Late-Stage Tuberculosis in C3HeB/FeJ Mice, J. Immunol., 2016, 196, 3 1293–1304
B. R. Becklund, K. S. Severson, S. V. Vang and H. F. DeLuca, UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production, Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 14 6418–6423
S. Gorman, N. M. Scott, D. H. Tan, C. E. Weeden, R. C. Tuckey, J. L. Bisley, et al., Acute erythemal ultraviolet radiation causes systemic immunosuppression in the absence of increased 25-hydroxyvitamin D3 levels in male mice, PLoS One, 2012, 7, 9 e46006
M. Ghoreishi, P. Bach, J. Obst, M. Komba, J. C. Fleet and J. P. Dutz, Expansion of antigen-specific regulatory T cells with the topical vitamin d analog calcipotriol, J. Immunol., 2009, 182, 10 6071–6078
C. R. Howson, Heliotherapy in Pulmonary Tuberculosis-Its Possibilities and Dangers, Calif. West. Med., 1928, 29, 1 25–30
W. B. Grant and E. Giovannucci, The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918–1919 influenza pandemic in the United States, Dermatoendocrinology, 2009, 1, 4 215–219
M. Hartley, S. Hoare, F. E. Lithander, R. E. Neale, P. H. Hart, S. Gorman, et al., Comparing the effects of sun exposure and vitamin D supplementation on vitamin D insufficiency, and immune and cardio-metabolic function: the Sun Exposure and Vitamin D Supplementation (SEDS) Study, BMC Public Health, 2015, 15, 115
K. Soontrapa, T. Honda, D. Sakata, C. Yao, T. Hirata, S. Hori, et al., Prostaglandin E2-prostaglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression, Proc. Natl. Acad. Sci. U. S. A., 2011, 108, 16 6668–6673
K. Loser, A. Mehling, S. Loeser, J. Apelt, A. Kuhn, S. Grabbe, et al., Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells, Nat. Med., 2006, 12, 12 1372–1379
S. N. Byrne, C. Beaugie, C. O’Sullivan, S. Leighton and G. M. Halliday, The immune-modulating cytokine and endogenous Alarmin interleukin-33 is upregulated in skin exposed to inflammatory UVB radiation, Am. J. Pathol., 2011, 179, 1 211–222
R. Chacon-Salinas, L. Chen, A. D. Chavez-Blanco, A. Y. Limon-Flores, Y. Ma and S. E. Ullrich, An essential role for platelet-activating factor in activating mast cell migration following ultraviolet irradiation, J. Leukoc. Biol., 2014, 95, 1 139–148
S. N. Byrne, A. Y. Limon-Flores and S. E. Ullrich, Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression, J. Immunol., 2008, 180, 7 4648–4655
R. Chacon-Salinas, A. Y. Limon-Flores, A. D. Chavez-Blanco, A. Gonzalez-Estrada and S. E. Ullrich, Mast cell-derived IL-10 suppresses germinal center formation by affecting T follicular helper cell function, J. Immunol., 2011, 186, 1 25–31
S. N. Byrne and G. M. Halliday, B cells activated in lymph nodes in response to ultraviolet irradiation or by interleukin-10 inhibit dendritic cell induction of immunity, J. Invest. Dermatol., 2005, 124, 3 570–578
T. Schwarz and A. Schwarz, Molecular mechanisms of ultraviolet radiation-induced immunosuppression, Eur. J. Cell Biol., 2011, 90, 6–7 560–564
A. Maeda, S. Beissert, T. Schwarz and A. Schwarz, Phenotypic and functional characterization of ultraviolet radiation-induced regulatory T cells, J. Immunol., 2008, 180, 5 3065–3071
A. M. Moodycliffe, D. Nghiem, G. Clydesdale and S. E. Ullrich, Immune suppression and skin cancer development: regulation by NKT cells, Nat. Immunol., 2000, 1, 6 521–525
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Abhimanyu, Coussens, A.K. The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease. Photochem Photobiol Sci 16, 314–338 (2017). https://doi.org/10.1039/c6pp00355a
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1039/c6pp00355a