Abstract
Sexual dimorphisms account for differences in clinical manifestations or incidence of infectious or autoimmune diseases and malignancy between females and males. Females develop enhanced innate and adaptive immune responses than males and are less susceptible to many infections of bacterial, viral, parasitic, and fungal origin and malignancies but in contrast, they are more prone to develop autoimmune diseases. The higher susceptibility to infections in males is observed from birth to adulthood, suggesting that sex chromosomes and not sex hormones have a major role in sexual dimorphism in innate immunity. Sex-based regulation of immune responses ultimately contributes to age-related disease development and life expectancy. Differences between males and females have been described in the expression of pattern recognition receptors of the innate immune response and in the functional responses of phagocytes and antigen presenting cells. Different factors have been shown to account for the sex-based disparity in immune responses, including genetic factors and hormonal mediators, which contribute independently to dimorphism in the innate immune response. For instance, several genes encoding for innate immune molecules are located on the X chromosome. In addition, estrogen and/or testosterone have been reported to modulate the differentiation, maturation, lifespan, and effector functions of innate immune cells, including neutrophils, macrophages, natural killer cells, and dendritic cells. In this review, we will focus on differences between males and females in innate immunity, which represents the first line of defense against pathogens and plays a fundamental role in the activation, regulation, and orientation of the adaptive immune response.
Similar content being viewed by others
References
Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16(10):626–638. https://doi.org/10.1038/nri.2016.90
Fish EN (2008) The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol 8(9):737–744. https://doi.org/10.1038/nri2394
Libert C, Dejager L, Pinheiro I (2010) The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol 10(8):594–604. https://doi.org/10.1038/nri2815
vom Steeg LG, Klein SL (2016) SeXX matters in infectious disease pathogenesis. PLoS Pathog 12(2):e1005374. https://doi.org/10.1371/journal.ppat.1005374
Giefing-Kroll C, Berger P, Lepperdinger G, Grubeck-Loebenstein B (2015) How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging Cell 14(3):309–321. https://doi.org/10.1111/acel.12326
Hill-Burns EM, Clark AG (2009) X-linked variation in immune response in Drosophila melanogaster. Genetics 183(4):1477–1491. https://doi.org/10.1534/genetics.108.093971
Jaillon S, Ponzetta A, Magrini E, Barajon I, Barbagallo M et al (2016) Fluid phase recognition molecules in neutrophil-dependent immune responses. Semin Immunol 28(2):109–118. https://doi.org/10.1016/j.smim.2016.03.005
Bottazzi B, Doni A, Garlanda C, Mantovani A (2010) An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu Rev Immunol 28:157–183
Torcia MG, Nencioni L, Clemente AM, Civitelli L, Celestino I et al (2012) Sex differences in the response to viral infections: TLR8 and TLR9 ligand stimulation induce higher IL10 production in males. PLoS One 7(6):e39853. https://doi.org/10.1371/journal.pone.0039853
Asai K, Hiki N, Mimura Y, Ogawa T, Unou K et al (2001) Gender differences in cytokine secretion by human peripheral blood mononuclear cells: role of estrogen in modulating LPS-induced cytokine secretion in an ex vivo septic model. Shock 16(5):340–343
Berghofer B, Frommer T, Haley G, Fink L, Bein G et al (2006) TLR7 ligands induce higher IFN-alpha production in females. J Immunol 177(4):2088–2096
Meier A, Chang JJ, Chan ES, Pollard RB, Sidhu HK et al (2009) Sex differences in the toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat Med 15(8):955–959. https://doi.org/10.1038/nm.2004
Seillet C, Laffont S, Tremollieres F, Rouquie N, Ribot C et al (2012) The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor alpha signaling. Blood 119(2):454–464. https://doi.org/10.1182/blood-2011-08-371831
Seillet C, Rouquie N, Foulon E, Douin-Echinard V, Krust A et al (2013) Estradiol promotes functional responses in inflammatory and steady-state dendritic cells through differential requirement for activation function-1 of estrogen receptor alpha. J Immunol 190(11):5459–5470. https://doi.org/10.4049/jimmunol.1203312
Griesbeck M, Ziegler S, Laffont S, Smith N, Chauveau L et al (2015) Sex Differences in plasmacytoid dendritic cell levels of IRF5 drive higher IFN-alpha production in women. J Immunol 195(11):5327–5336. https://doi.org/10.4049/jimmunol.1501684
Schoenemeyer A, Barnes BJ, Mancl ME, Latz E, Goutagny N et al (2005) The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling. J Biol Chem 280(17):17005–17012. https://doi.org/10.1074/jbc.M412584200
Laffont S, Rouquie N, Azar P, Seillet C, Plumas J et al (2014) X-Chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR7-mediated IFN-alpha production of plasmacytoid dendritic cells from women. J Immunol 193(11):5444–5452. https://doi.org/10.4049/jimmunol.1303400
Marriott I, Bost KL, Huet-Hudson YM (2006) Sexual dimorphism in expression of receptors for bacterial lipopolysaccharides in murine macrophages: a possible mechanism for gender-based differences in endotoxic shock susceptibility. J Reprod Immunol 71(1):12–27. https://doi.org/10.1016/j.jri.2006.01.004
Scotland RS, Stables MJ, Madalli S, Watson P, Gilroy DW (2011) Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice. Blood 118(22):5918–5927. https://doi.org/10.1182/blood-2011-03-340281
McGowan JE Jr, Barnes MW, Finland M (1975) Bacteremia at Boston City Hospital: occurrence and mortality during 12 selected years (1935-1972), with special reference to hospital-acquired cases. J Infect Dis 132(3):316–335
Bone RC (1992) Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome). JAMA 268(24):3452–3455
Fourrier F, Jallot A, Leclerc L, Jourdain M, Racadot A et al (1994) Sex steroid hormones in circulatory shock, sepsis syndrome, and septic shock. Circ Shock 43(4):171–178
Barrow RE, Herndon DN (1990) Incidence of mortality in boys and girls after severe thermal burns. Surg Gynecol Obstet 170(4):295–298
Schroder J, Kahlke V, Staubach KH, Zabel P, Stuber F (1998) Gender differences in human sepsis. Arch Surg 133(11):1200–1205
Kisat M, Villegas CV, Onguti S, Zafar SN, Latif A et al (2013) Predictors of sepsis in moderately severely injured patients: an analysis of the National Trauma Data Bank. Surg Infect 14(1):62–68. https://doi.org/10.1089/sur.2012.009
Offner PJ, Moore EE, Biffl WL (1999) Male gender is a risk factor for major infections after surgery. Arch Surg 134(9):935–938 discussion 938-940
Reade MC, Yende S, D'Angelo G, Kong L, Kellum JA et al (2009) Differences in immune response may explain lower survival among older men with pneumonia. Crit Care Med 37(5):1655–1662. https://doi.org/10.1097/CCM.0b013e31819da853
Angele MK, Pratschke S, Hubbard WJ, Chaudry IH (2014) Gender differences in sepsis: cardiovascular and immunological aspects. Virulence 5(1):12–19. https://doi.org/10.4161/viru.26982
Newsome CT, Flores E, Ayala A, Gregory S, Reichner JS (2011) Improved antimicrobial host defense in mice following poly-(1,6)-beta-D-glucopyranosyl-(1,3)-beta-D-glucopyranose glucan treatment by a gender-dependent immune mechanism. Clin Vaccine Immunol 18(12):2043–2049. https://doi.org/10.1128/CVI.05202-11
Christeff N, Benassayag C, Carli-Vielle C, Carli A, Nunez EA (1988) Elevated oestrogen and reduced testosterone levels in the serum of male septic shock patients. J Steroid Biochem 29(4):435–440
Drechsler S, Weixelbaumer K, Raeven P, Jafarmadar M, Khadem A et al (2012) Relationship between age/gender-induced survival changes and the magnitude of inflammatory activation and organ dysfunction in post-traumatic sepsis. PLoS One 7(12):e51457. https://doi.org/10.1371/journal.pone.0051457
Mantovani A, Cassatella MA, Costantini C, Jaillon S (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11(8):519–531
Jaillon S, Galdiero MR, Del Prete D, Cassatella MA, Garlanda C et al (2013) Neutrophils in innate and adaptive immunity. Semin Immunopathol 35(4):377–394. https://doi.org/10.1007/s00281-013-0374-8
Wirths S, Bugl S, Kopp HG (2014) Neutrophil homeostasis and its regulation by danger signaling. Blood 123(23):3563–3566. https://doi.org/10.1182/blood-2013-11-516260
Scapini P, Cassatella MA (2014) Social networking of human neutrophils within the immune system. Blood 124(5):710–719. https://doi.org/10.1182/blood-2014-03-453217
Marini O, Costa S, Bevilacqua D, Calzetti F, Tamassia N et al (2017) Mature CD10+ and immature CD10− neutrophils present in G-CSF-treated donors display opposite effects on T cells. Blood 129(10):1343–1356. https://doi.org/10.1182/blood-2016-04-713206
Coffelt SB, Wellenstein MD, de Visser KE (2016) Neutrophils in cancer: neutral no more. Nat Rev Cancer 16(7):431–446. https://doi.org/10.1038/nrc.2016.52
Bouman A, Heineman MJ, Faas MM (2005) Sex hormones and the immune response in humans. Hum Reprod Update 11(4):411–423. https://doi.org/10.1093/humupd/dmi008
Jeannin P, Jaillon S, Delneste Y (2008) Pattern recognition receptors in the immune response against dying cells. Curr Opin Immunol 20(5):530–537
Kaplan MJ (2011) Neutrophils in the pathogenesis and manifestations of SLE. Nat Rev Rheumatol 7(12):691–699. https://doi.org/10.1038/nrrheum.2011.132
Molloy EJ, O'Neill AJ, Grantham JJ, Sheridan-Pereira M, Fitzpatrick JM et al (2003) Sex-specific alterations in neutrophil apoptosis: the role of estradiol and progesterone. Blood 102(7):2653–2659. https://doi.org/10.1182/blood-2003-02-0649
Chuang KH, Altuwaijri S, Li G, Lai JJ, Chu CY et al (2009) Neutropenia with impaired host defense against microbial infection in mice lacking androgen receptor. J Exp Med 206(5):1181–1199. https://doi.org/10.1084/jem.20082521
Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E et al (2015) Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 518(7540):547–551. https://doi.org/10.1038/nature13989
De Kleer I, Willems F, Lambrecht B, Goriely S (2014) Ontogeny of myeloid cells. Front Immunol 5:423. https://doi.org/10.3389/fimmu.2014.00423
Wynn TA, Chawla A, Pollard JW (2013) Macrophage biology in development, homeostasis and disease. Nature 496(7446):445–455. https://doi.org/10.1038/nature12034
Bain CC, Bravo-Blas A, Scott CL, Perdiguero EG, Geissmann F et al (2014) Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol 15(10):929–937. https://doi.org/10.1038/ni.2967
McGovern N, Schlitzer A, Gunawan M, Jardine L, Shin A et al (2014) Human dermal CD14(+) cells are a transient population of monocyte-derived macrophages. Immunity 41(3):465–477. https://doi.org/10.1016/j.immuni.2014.08.006
Molawi K, Wolf Y, Kandalla PK, Favret J, Hagemeyer N et al (2014) Progressive replacement of embryo-derived cardiac macrophages with age. J Exp Med 211(11):2151–2158. https://doi.org/10.1084/jem.20140639
Ter Horst R, Jaeger M, Smeekens SP, Oosting M, Swertz MA et al (2016) Host and environmental factors influencing individual human cytokine responses. Cell 167(4):1111–1124 e1113. https://doi.org/10.1016/j.cell.2016.10.018
Biswas SK, Mantovani A (2010) Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 11(10):889–896. https://doi.org/10.1038/ni.1937
Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122(3):787–795. https://doi.org/10.1172/JCI59643
Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8(12):958–969. https://doi.org/10.1038/nri2448
Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW et al (2014) Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41(1):14–20. https://doi.org/10.1016/j.immuni.2014.06.008
Mantovani A, Allavena P (2015) The interaction of anticancer therapies with tumor-associated macrophages. J Exp Med DOI. https://doi.org/10.1084/jem.20150295
Li K, Xu W, Guo Q, Jiang Z, Wang P et al (2009) Differential macrophage polarization in male and female BALB/c mice infected with coxsackievirus B3 defines susceptibility to viral myocarditis. Circ Res 105(4):353–364. https://doi.org/10.1161/CIRCRESAHA.109.195230
Melgert BN, Oriss TB, Qi Z, Dixon-McCarthy B, Geerlings M et al (2010) Macrophages: regulators of sex differences in asthma? Am J Respir Cell Mol Biol 42(5):595–603. https://doi.org/10.1165/rcmb.2009-0016OC
Galvan-Pena S, O'Neill LA (2014) Metabolic reprograming in macrophage polarization. Front Immunol 5:420. https://doi.org/10.3389/fimmu.2014.00420
Gubbels Bupp MR (2015) Sex, the aging immune system, and chronic disease. Cell Immunol 294(2):102–110. https://doi.org/10.1016/j.cellimm.2015.02.002
Klein SL, Jedlicka A, Pekosz A (2010) The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis 10(5):338–349. https://doi.org/10.1016/S1473-3099(10)70049-9
Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L et al (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331(6013):44–49. https://doi.org/10.1126/science.1198687
Hanna J, Goldman-Wohl D, Hamani Y, Avraham I, Greenfield C et al (2006) Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med 12(9):1065–1074
Carlino C, Stabile H, Morrone S, Bulla R, Soriani A et al (2008) Recruitment of circulating NK cells through decidual tissues: a possible mechanism controlling NK cell accumulation in the uterus during early pregnancy. Blood 111(6):3108–3115
Chistiakov DA, Orekhov AN, Sobenin IA, Bobryshev YV (2014) Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation. Front Physiol 5:279. https://doi.org/10.3389/fphys.2014.00279
Marshak-Rothstein A (2006) Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 6(11):823–835. https://doi.org/10.1038/nri1957
Ronnblom L, Eloranta ML, Alm GV (2006) The type I interferon system in systemic lupus erythematosus. Arthritis Rheum 54(2):408–420. https://doi.org/10.1002/art.21571
Whitacre CC (2001) Sex differences in autoimmune disease. Nat Immunol 2(9):777–780. https://doi.org/10.1038/ni0901-777
Ghosh S, Klein RS (2017) Sex drives dimorphic immune responses to viral infections. J Immunol 198(5):1782–1790. https://doi.org/10.4049/jimmunol.1601166
Sterling TR, Vlahov D, Astemborski J, Hoover DR, Margolick JB et al (2001) Initial plasma HIV-1 RNA levels and progression to AIDS in women and men. N Engl J Med 344(10):720–725. https://doi.org/10.1056/NEJM200103083441003
Beignon AS, McKenna K, Skoberne M, Manches O, DaSilva I et al (2005) Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. J Clin Invest 115(11):3265–3275. https://doi.org/10.1172/JCI26032
Tsao LC, Guo H, Jeffrey J, Hoxie JA, Su L (2016) CCR5 interaction with HIV-1 Env contributes to Env-induced depletion of CD4 T cells in vitro and in vivo. Retrovirology 13:22. https://doi.org/10.1186/s12977-016-0255-z
Pessach IM, Notarangelo LD (2009) X-linked primary immunodeficiencies as a bridge to better understanding X-chromosome related autoimmunity. J Autoimmun 33(1):17–24. https://doi.org/10.1016/j.jaut.2009.03.003
Bouma G, Burns SO, Thrasher AJ (2009) Wiskott-Aldrich Syndrome: immunodeficiency resulting from defective cell migration and impaired immunostimulatory activation. Immunobiology 214(9–10):778–790. https://doi.org/10.1016/j.imbio.2009.06.009
Hannah MF, Bajic VB, Klein SL (2008) Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats. Brain Behav Immun 22(4):503–516. https://doi.org/10.1016/j.bbi.2007.10.005
Bjornstrom L, Sjoberg M (2005) Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol 19(4):833–842. https://doi.org/10.1210/me.2004-0486
Ray A, Prefontaine KE, Ray P (1994) Down-modulation of interleukin-6 gene expression by 17 beta-estradiol in the absence of high affinity DNA binding by the estrogen receptor. J Biol Chem 269(17):12940–12946
Stein B, Yang MX (1995) Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Mol Cell Biol 15(9):4971–4979
Palaszynski KM, Smith DL, Kamrava S, Burgoyne PS, Arnold AP et al (2005) A yin-yang effect between sex chromosome complement and sex hormones on the immune response. Endocrinology 146(8):3280–3285. https://doi.org/10.1210/en.2005-0284
Wichmann MW, Zellweger R, DeMaso CM, Ayala A, Chaudry IH (1996) Mechanism of immunosuppression in males following trauma-hemorrhage. Critical role of testosterone. Arch Surg 131(11):1186–1191 discussion 1191-1182
Trigunaite A, Dimo J, Jorgensen TN (2015) Suppressive effects of androgens on the immune system. Cell Immunol 294(2):87–94. https://doi.org/10.1016/j.cellimm.2015.02.004
Miyagi M, Aoyama H, Morishita M, Iwamoto Y (1992) Effects of sex hormones on chemotaxis of human peripheral polymorphonuclear leukocytes and monocytes. J Periodontol 63(1):28–32. https://doi.org/10.1902/jop.1992.63.1.28
Robinson DP, Hall OJ, Nilles TL, Bream JH, Klein SL (2014) 17beta-estradiol protects females against influenza by recruiting neutrophils and increasing virus-specific CD8 T cell responses in the lungs. J Virol 88(9):4711–4720. https://doi.org/10.1128/JVI.02081-13
Lasarte S, Samaniego R, Salinas-Munoz L, Guia-Gonzalez MA, Weiss LA et al (2016) Sex hormones coordinate neutrophil immunity in the vagina by controlling chemokine gradients. J Infect Dis 213(3):476–484. https://doi.org/10.1093/infdis/jiv402
Deitch EA, Ananthakrishnan P, Cohen DB, Xu DZ, Feketeova E et al (2006) Neutrophil activation is modulated by sex hormones after trauma-hemorrhagic shock and burn injuries. Am J Physiol Heart Circ Physiol 291(3):H1456–H1465. https://doi.org/10.1152/ajpheart.00694.2005
Angele MK, Schwacha MG, Ayala A, Chaudry IH (2000) Effect of gender and sex hormones on immune responses following shock. Shock 14(2):81–90
Rettew JA, Huet-Hudson YM, Marriott I (2008) Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity. Biol Reprod 78(3):432–437. https://doi.org/10.1095/biolreprod.107.063545
Rettew JA, Huet YM, Marriott I (2009) Estrogens augment cell surface TLR4 expression on murine macrophages and regulate sepsis susceptibility in vivo. Endocrinology 150(8):3877–3884. https://doi.org/10.1210/en.2009-0098
Bouman A, Schipper M, Heineman MJ, Faas MM (2004) Gender difference in the non-specific and specific immune response in humans. Am J Reprod Immunol 52(1):19–26. https://doi.org/10.1111/j.1600-0897.2004.00177.x
Hughes GC, Thomas S, Li C, Kaja MK, Clark EA (2008) Cutting edge: progesterone regulates IFN-alpha production by plasmacytoid dendritic cells. J Immunol 180(4):2029–2033
Tora L, White J, Brou C, Tasset D, Webster N et al (1989) The human estrogen receptor has two independent nonacidic transcriptional activation functions. Cell 59(3):477–487
Lanzavecchia A, Sallusto F (2001) The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics. Curr Opin Immunol 13(3):291–298
Paharkova-Vatchkova V, Maldonado R, Kovats S (2004) Estrogen preferentially promotes the differentiation of CD11c+ CD11b(intermediate) dendritic cells from bone marrow precursors. J Immunol 172(3):1426–1436
Siracusa MC, Overstreet MG, Housseau F, Scott AL, Klein SL (2008) 17beta-estradiol alters the activity of conventional and IFN-producing killer dendritic cells. J Immunol 180(3):1423–1431
Bengtsson AK, Ryan EJ, Giordano D, Magaletti DM, Clark EA (2004) 17beta-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells. Blood 104(5):1404–1410. https://doi.org/10.1182/blood-2003-10-3380
Baden R, Rockstroh JK, Buti M (2014) Natural history and management of hepatitis C: does sex play a role? J Infect Dis 209(Suppl 3):S81–S85. https://doi.org/10.1093/infdis/jiu057
Kamada M, Irahara M, Maegawa M, Ohmoto Y, Takeji T et al (2001) Postmenopausal changes in serum cytokine levels and hormone replacement therapy. Am J Obstet Gynecol 184(3):309–314. https://doi.org/10.1067/mob.2001.109940
Vural P, Akgul C, Canbaz M (2006) Effects of hormone replacement therapy on plasma pro-inflammatory and anti-inflammatory cytokines and some bone turnover markers in postmenopausal women. Pharmacol Res 54(4):298–302. https://doi.org/10.1016/j.phrs.2006.06.006
Salamonsen LA, Dimitriadis E, Jones RL, Nie G (2003) Complex regulation of decidualization: a role for cytokines and proteases—a review. Placenta 24(Suppl A):S76–S85
Garlanda C, Maina V, Martinez de la Torre Y, Nebuloni M, Locati M (2008) Inflammatory reaction and implantation: the new entries PTX3 and D6. Placenta 29(Suppl B):129–134
Leonard S, Murrant C, Tayade C, van den Heuvel M, Watering R et al (2006) Mechanisms regulating immune cell contributions to spiral artery modification—facts and hypotheses—a review. Placenta 27(Suppl A):S40–S46
Redman CW, Sargent IL (2005) Latest advances in understanding preeclampsia. Science 308(5728):1592–1594
Graham C, Chooniedass R, Stefura WP, Becker AB, Sears MR et al (2017) In vivo immune signatures of healthy human pregnancy: inherently inflammatory or anti-inflammatory? PLoS One 12(6):e0177813. https://doi.org/10.1371/journal.pone.0177813
PrabhuDas M, Bonney E, Caron K, Dey S, Erlebacher A et al (2015) Immune mechanisms at the maternal-fetal interface: perspectives and challenges. Nat Immunol 16(4):328–334. https://doi.org/10.1038/ni.3131
Salamonsen LA, Zhang J, Brasted M (2002) Leukocyte networks and human endometrial remodelling. J Reprod Immunol 57(1–2):95–108
Martinez de la Torre Y, Buracchi C, Borroni EM, Dupor J, Bonecchi R et al (2007) Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6. Proc Natl Acad Sci U S A 104(7):2319–2324
Salustri A, Garlanda C, Hirsch E, De Acetis M, Maccagno A et al (2004) PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development 131(7):1577–1586
Cetin I, Cozzi V, Pasqualini F, Nebuloni M, Garlanda C et al (2006) Elevated maternal levels of the long pentraxin 3 (PTX3) in preeclampsia and intrauterine growth restriction. Am J Obstet Gynecol 194(5):1347–1353
Cozzi V, Garlanda C, Nebuloni M, Maina V, Martinelli A et al (2012) PTX3 as a potential endothelial dysfunction biomarker for severity of preeclampsia and IUGR. Placenta 33(12):1039–1044. https://doi.org/10.1016/j.placenta.2012.09.009
Dorak MT, Karpuzoglu E (2012) Gender differences in cancer susceptibility: an inadequately addressed issue. Front Genet 3:268. https://doi.org/10.3389/fgene.2012.00268
Morrison BA, Ucisik-Akkaya E, Flores H, Alaez C, Gorodezky C et al (2010) Multiple sclerosis risk markers in HLA-DRA, HLA-C, and IFNG genes are associated with sex-specific childhood leukemia risk. Autoimmunity 43(8):690–697. https://doi.org/10.3109/08916930903567492
Do TN, Ucisik-Akkaya E, Davis CF, Morrison BA, Dorak MT (2010) An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males. Biochim Biophys Acta 1802(2):292–300. https://doi.org/10.1016/j.bbadis.2009.10.015
Adamaki M, Lambrou GI, Athanasiadou A, Tzanoudaki M, Vlahopoulos S et al (2013) Implication of IRF4 aberrant gene expression in the acute leukemias of childhood. PLoS One 8(8):e72326. https://doi.org/10.1371/journal.pone.0072326
Yuan Y, Liu L, Chen H, Wang Y, Xu Y et al (2016) Comprehensive characterization of molecular differences in cancer between male and female patients. Cancer Cell 29(5):711–722. https://doi.org/10.1016/j.ccell.2016.04.001
Kreuzer M, Boffetta P, Whitley E, Ahrens W, Gaborieau V et al (2000) Gender differences in lung cancer risk by smoking: a multicentre case-control study in Germany and Italy. Br J Cancer 82(1):227–233. https://doi.org/10.1054/bjoc.1999.0904
Stabile LP, Davis AL, Gubish CT, Hopkins TM, Luketich JD et al (2002) Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res 62(7):2141–2150
Weige CC, Allred KF, Allred CD (2009) Estradiol alters cell growth in nonmalignant colonocytes and reduces the formation of preneoplastic lesions in the colon. Cancer Res 69(23):9118–9124. https://doi.org/10.1158/0008-5472.CAN-09-2348
Naugler WE, Sakurai T, Kim S, Maeda S, Kim K et al (2007) Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317(5834):121–124. https://doi.org/10.1126/science.1140485
Hartwell HJ, Petrosky KY, Fox JG, Horseman ND, Rogers AB (2014) Prolactin prevents hepatocellular carcinoma by restricting innate immune activation of c-Myc in mice. Proc Natl Acad Sci U S A 111(31):11455–11460. https://doi.org/10.1073/pnas.1404267111
Yan C, Yang Q, Gong Z (2017) Tumor-associated neutrophils and macrophages promote gender disparity in hepatocellular carcinoma in zebrafish. Cancer Res 77(6):1395–1407. https://doi.org/10.1158/0008-5472.CAN-16-2200
Funding
The contribution of Ministero della Salute (RF-2013-02355470), Ministry of Education, University and Research (PRIN 2015YYKPNN), and the Associazione Italiana Ricerca sul Cancro (MFAG 2016 ID 18475) is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflicts of Interest
The authors declare that they have no conflict of interest.
Ethical Approval and Informed Consent
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
About this article
Cite this article
Jaillon, S., Berthenet, K. & Garlanda, C. Sexual Dimorphism in Innate Immunity. Clinic Rev Allerg Immunol 56, 308–321 (2019). https://doi.org/10.1007/s12016-017-8648-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12016-017-8648-x