MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection.
J Virol
; 84(24): 12713-22, 2010 Dec.
Article
en En
| MEDLINE
| ID: mdl-20943980
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.
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Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Infecciones por Orthomyxoviridae
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Subtipo H1N1 del Virus de la Influenza A
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Subtipo H5N2 del Virus de la Influenza A
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Factor 88 de Diferenciación Mieloide
Límite:
Animals
Idioma:
En
Revista:
J Virol
Año:
2010
Tipo del documento:
Article