Mechanisms of Lymphocyte Activation and Immune Regulation X

Volume 560 of the series Advances in Experimental Medicine and Biology pp 1-9

TIR Domain-Containing Adaptors Regulate TLR Signaling Pathways

  • Masahiro YamamotoAffiliated withDepartment of Host Defense, Research Institute for Microbial Diseases, Osaka University
  • , Shizuo AkiraAffiliated withDepartment of Host Defense, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Host Defense, Research Institute for Microbial Diseases, Osaka UniversityERATO

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Against invading microorganisms, vertebrates including mammals develop innate immune systems, which are activated by microbial components possessing conserved structures called pathogen associated molecular patterns (PAMPs); including bacterial cell wall components, and viral genomic DNA and RNA. PAMPs are recognized by pattern recognition receptors mainly expressing on immune responsive cells. Toll-like receptors (TLRS) are an example of pattern recognition receptors, and TLR family members are conserved among mammals. To date, 10 and 12 TLRs have been reported in human and mouse, respectively. Almost all TLRs have been shown to recognize PAMPs; TLR2 is the receptor for peptidoglycan and lipoprotein, including bacterial lipoprotein (BLP) and mycoplasmal lipoprotein (MALP-2). Especially, BLP and MALP-2 are reportedly recognized in the functional heterodimeric association of TLR2 with TLRl and TLR6, respectively. TLR4 is involved in the recognition of a gram-negative cell wall component, lipopolysaccharide (LPS). TLR5 is a receptor for flagellin, a component of bacterial flagella. TLR3 and TLR9 are receptors for double-stranded (ds) RNA and unmethylated CpG DNA, respectively. Although the natural ligand for TLR7 is yet to be identified, the receptor has been shown to recognize imidazoquid or its derivative, R- 848. Since they are utilized in the treatment of genital warts caused by human papilomavirus, the ligand for TLR7 seems to be a component of viruses. Thus, accumulating evidence clearly demonstrates that TLRs serve as pattern recognition receptors to detect invading microbes (Figure 1).