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

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.

• Authors: Sang-Uk Seo, Hyung-Joon Kwon, Joo-Hye Song, Young-Ho Byun, Baik Lin Seong, Taro Kawai, Shizuo Akira, Mi-Na Kweon
• Journal: Journal of virology (J Virol) Vol. 84 Issue 24 Pg. 12713-22 (Dec 2010) ISSN: 1098-5514 [Electronic] United States
• PMID: 20943980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Adaptor Proteins, Vesicular Transport
• Antibodies, Viral
• IPS-1 protein, mouse
• Membrane Glycoproteins
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• TICAM-1 protein, mouse
• TLR3 protein, mouse
• Tlr7 protein, mouse
• Toll-Like Receptor 3
• Toll-Like Receptor 7

Topics

• Adaptor Proteins, Signal Transducing (physiology)
• Adaptor Proteins, Vesicular Transport (physiology)
• Animals
• Antibodies, Viral (immunology)
• Female
• Immunity, Innate
• Influenza A Virus, H1N1 Subtype (pathogenicity)
• Influenza A Virus, H5N2 Subtype (pathogenicity)
• Male
• Membrane Glycoproteins (physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Differentiation Factor 88 (physiology)
• Orthomyxoviridae Infections (immunology, prevention & control, virology)
• Signal Transduction (immunology)
• T-Lymphocytes (immunology)
• Toll-Like Receptor 3 (physiology)
• Toll-Like Receptor 7 (physiology)