Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades.
MyD88 is an adaptor molecule essential for signaling via the Toll-like receptor (TLR)/IL-1 receptor family. TLR4 is a member of the TLR family and a point mutation in the Tlr4 gene causes hyporesponsiveness to lipopolysaccharide (LPS) in C3H/HeJ mice. We have previously shown that both TLR4- and MyD88-deficient mice are hyporesponsive to LPS. In this study we examined the responsiveness of these two knockout mice to various bacterial cell wall components. Cells from TLR4-deficient mice responded to several kinds of LPS, peptidoglycan and crude cell wall preparation from Gram-positive bacteria and mycobacterial lysates. In contrast, macrophages and splenocytes from MyD88-deficient mice did not respond to any of the bacterial components we tested. These results show that MyD88 is essential for the cellular response to bacterial cell wall components.
Takeuchi
O
O
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and CREST of Japan Science and Technology Corp., 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Takeda
K
K
Hoshino
K
K
Adachi
O
O
Ogawa
T
T
Akira
S
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000276:immunology*; D029721:Drosophila Proteins; D006090:Gram-Negative Bacteria / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009161:Mycobacterium / Q000276:immunology; D053594:Myeloid Differentiation Factor 88; D010457:Peptidoglycan / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors