tetano
Editor, Senior Moderator
J Virol. 2010 Oct 13. [Epub ahead of print]
MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection.
Seo SU, Kwon HJ, Song JH, Byun YH, Seong BL, Kawai T, Akira S, Kweon MN.
Mucosal Immunology Section, International Vaccine Institute, Seoul, South Korea; Department of Biotechnology, College of Engineering, Yonsei University, Seoul, South Korea; and Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, Japan.
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 (PR8, H1N1), we adopted 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 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 infection than the B6 mice but were fully protected against homologous (H1N1) and heterosubtypic (H5N2) secondary infection when primed with a non-lethal 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.
http://www.ncbi.nlm.nih.gov/pubmed/20943980
MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection.
Seo SU, Kwon HJ, Song JH, Byun YH, Seong BL, Kawai T, Akira S, Kweon MN.
Mucosal Immunology Section, International Vaccine Institute, Seoul, South Korea; Department of Biotechnology, College of Engineering, Yonsei University, Seoul, South Korea; and Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, Japan.
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 (PR8, H1N1), we adopted 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 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 infection than the B6 mice but were fully protected against homologous (H1N1) and heterosubtypic (H5N2) secondary infection when primed with a non-lethal 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.
http://www.ncbi.nlm.nih.gov/pubmed/20943980