期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.588382
关键词
IL-17A; IFN-α 2; chikungunya virus; IRF5; 7; inflammation; mice
类别
资金
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R15AI35893]
- National Institute of General Medical Sciences [P20 GM103476]
Interferons (IFNs) are the key components of innate immunity and are crucial for host defense against viral infections. Here, we report a novel role of interleukin-17A (IL-17A) in inhibiting IFN-alpha 2 expression thus promoting chikungunya virus (CHIKV) infection. CHIKV infected IL-17A deficient (Il17a(-/-) ) mice expressed a higher level of IFN-alpha 2 and developed diminished viremia and milder footpad swelling in comparison to wild-type (WT) control mice, which was also recapitulated in IL-17A receptor-deficient (Il17ra(-/-) ) mice. Interestingly, IL-17A selectively blocked IFN-alpha 2 production during CHIKV, but not West Nile virus (WNV) or Zika virus (ZIKV), infections. Recombinant IL-17A treatment inhibited CHIKV-induced IFN-alpha 2 expression and enhanced CHIKV replication in both human and mouse cells. We further found that IL-17A inhibited IFN-alpha 2 production by modulating the expression of Interferon Regulatory Factor-5 (IRF-5), IRF-7, IFN-stimulated gene 49 (ISG-49), and Mx1 expression during CHIKV infection. Neutralization of IL-17A in vitro leads to the increase of the expression of these antiviral molecules and decrease of CHIKV replication. Collectively, these results suggest a novel function of IL-17A in inhibiting IFN-alpha 2-mediated antiviral responses during CHIKV infection, which may have broad implications in viral infections and other inflammatory diseases.
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