Abstract
We previously reported that the Vibrio vulnificus hemolysin A (VvhA) protein elicited good immune protection and could effectively control V. vulnificus infection in mice. However, its molecular mechanism remains unknown. We hypothesized that hemolysin A induces an immunoprotective response via IL-21 regulation. To demonstrate this, IL-21 expression in mice was regulated by injecting either specific antibodies or rIL-21, and the immune response was evaluated by flow cytometry. Our results suggested that IL-21 enhances immune protection by inducing a T follicular helper cell and germinal center B cell response. We used RNA-seq to explore molecular mechanisms and identified 10 upregulated and 32 downregulated genes involved in IL-21-upregulated protection. Gene Ontology analysis and pathway analysis of the differentially expressed genes were also performed. Our findings indicate that IL-21 can enhance the immune protection effect of the VvhA protein and may serve as a novel strategy for enhancing the immune protection effect of protein vaccines.
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Acknowledgements
We thank Professor Sang Ho Choi for kindly providing the V. vulnificus M06-24/O strain.
Funding
This study was funded by the Natural Science Foundation of Shandong Province (No. ZR2021MC137) and the Dean Foundation (No. 2021MS02).
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Ke-Na Sun, Fei Huang, Jing Wu, and Cheng-Jin Hu. The first draft of the manuscript was written by Xiao-Fei Liu and Ming-Yi Wang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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All animal experiments were approved by the Animal Ethics and Experimental Committee of the 960th Hospital of the PLA Joint Logistics Support Force.
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Sun, KN., Huang, F., Wang, MY. et al. IL-21 Enhances the Immune Protection Induced by the Vibrio vulnificus Hemolysin A Protein. Inflammation 45, 1496–1506 (2022). https://doi.org/10.1007/s10753-022-01632-1
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DOI: https://doi.org/10.1007/s10753-022-01632-1