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

Research output: Contribution to journalArticle

58 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 1

Fingerprint

Influenza A virus
Virus Diseases
Coinfection
Orthomyxoviridae
mice
infection
Toll-Like Receptors
cytokines
T-lymphocytes
Cytokines
Viruses
T-Lymphocytes
viruses
receptors
Adaptive Immunity
granulocytes
Granulocytes
Innate Immunity
Immunoglobulin A
Immunoglobulin G

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Seo, Sang Uk ; Kwon, Hyung Joon ; Song, Joo Hye ; Byun, Young Ho ; Seong, Baik Lin ; Kawai, Taro ; Akira, Shizuo ; Kweon, Mi Na. / MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection. In: Journal of Virology. 2010 ; Vol. 84, No. 24. pp. 12713-12722.
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MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection. / Seo, Sang Uk; Kwon, Hyung Joon; Song, Joo Hye; Byun, Young Ho; Seong, Baik Lin; Kawai, Taro; Akira, Shizuo; Kweon, Mi Na.

In: Journal of Virology, Vol. 84, No. 24, 01.12.2010, p. 12713-12722.

Research output: Contribution to journalArticle

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AU - Seo, Sang Uk

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AU - Kweon, Mi Na

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