Shizuo Akira
Osaka University
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Primary Section: 43, Immunology and Inflammation Membership Type:
International Member
(elected 2009)
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Research Interests
Based on an unexpected finding that MyD88 knockout mice are unresponsive to lipopolysaccharide (LPS) of Gram-negative bacteria, I entered into research on innate immunity. By generating TLR family knockout mice, I identified ligands of many TLR members in addition to LPS receptor. Particularly, the identification of CpG DNA (pathogen-derived DNA) receptor as TLR9 is highly appreciated. This finding established a link between two arms of innate and acquired immunities. This result showed for the first time that TLRs are involved in viral recognition, and their recognition depends on the structure of nucleic acid. Until TLR ligands were identified, the response to all TLR ligands was considered to be identical and entirely dependent on MyD88. However, I showed for the first time the presence of MyD88-indepdent pathway in TLR signaling and showed that another adapter he named TRIF is involved in the MyD88-independent pathway. I demonstrated that the difference in signaling pathway among TLRs is due to selective usage of adaptor molecules such as MyD88 and TRIF. Recently, I showed that pathogen-derived RNA is recognized by cytoplasmic receptor family, besides TLRs, and clarified the molecular mechanism of antiviral response against RNA viruses.
