The role of Toll-like receptors and MyD88 in innate immune responses.
Toll-like receptors (TLRs) are phylogenetically conserved receptors that recognize pathogen associated molecular patterns (PAMPS). We previously generated mice lacking TLR2 and TLR4 and showed the differential role of TLR2 and TLR4 in microbial recognition. TLR4 functions as the transmembrane component of the lipopolysaccharide (LPS) receptor, while TLR2 recognizes peptidoglycan from Gram-positive bacteria and lipoprotein. We also generated mice lacking MyD88, an adaptor involved in IL-1R/TLR signalings. The responses to a variety of bacterial components were completely abrogated in MyD88-deficient cells. However, unlike the signaling mediated by other bacterial components such as lipoprotein and bacterial DNA, activation of NF-kappaB and MAP kinases was induced in response to LPS even in the absence of MyD88, which indicates the existence of a MyD88-independent pathway. We have recently found that the MyD88-independent pathway is involved in LPS-induced maturation of dendritic cells (DCs).
Akira
S
S
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. sakira@biken.osaka-u.ac.jp
Hoshino
K
K
Kaisho
T
T
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D029721:Drosophila Proteins; D008070:Lipopolysaccharides / Q000633:toxicity; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; C408982:CPG-oligonucleotide; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors