MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection

Sang Uk Seo, Hyung Joon Kwon, Joo Hye Song, Young Ho Byun, Baik Lin Seong, Taro Kawai, Shizuo Akira, Mi Na Kweon

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63 Citations (Scopus)

Abstract

Recent studies have revealed that innate immunity is involved in the development of adaptive immune responses; however, its role in protection is not clear. In order to elucidate the exact role of Toll-like receptor (TLR) or RIG-I-like receptor (RLR) signaling on immunogenicity and protective efficacy against influenza A virus infection (A/PR/8/34 [PR8]; H1N1), we adapted several innate signal-deficient mice (e.g., TRIF-/-, MyD88-/-, MyD88-/- TRIF-/-, TLR3-/- TLR7-/-, and IPS-1-/-). In this study, we found that MyD88 signaling was required for recruitment of CD11b+ granulocytes, production of early inflammatory cytokines, optimal proliferation of CD4 T cells, and production of Th1 cytokines by T cells. However, PR8 virus-specific IgG and IgA antibody levels in both systemic and mucosal compartments were normal in TLR- and RLR-deficient mice. To further assess the susceptibility of these mice to influenza virus infection, protective efficacy was determined after primary or secondary lethal challenge. We found that MyD88-/- and MyD88 -/- TRIF-/- mice were more susceptible to primary influenza virus infection than the B6 mice but were fully protected against homologous (H1N1) and heterosubtypic (H5N2) secondary infection when primed with a nonlethal dose of PR8 virus. Taken together, these results show that MyD88 signaling plays an important role for resisting primary influenza virus infection but is dispensable for protection against a secondary lethal challenge.

Original languageEnglish
Pages (from-to)12713-12722
Number of pages10
JournalJournal of Virology
Volume84
Issue number24
DOIs
Publication statusPublished - 2010 Dec

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Seo, S. U., Kwon, H. J., Song, J. H., Byun, Y. H., Seong, B. L., Kawai, T., Akira, S., & Kweon, M. N. (2010). MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection. Journal of Virology, 84(24), 12713-12722. https://doi.org/10.1128/JVI.01675-10