Essential role for TLR4 and MyD88 in the development of chronic intestinal nematode infection.
Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper 2 type response involving IL-4 and IL-13. Here we show that Th1 response-associated susceptibility is dependent on activation signals mediated by MyD88 and Toll-like receptor 4 (TLR4). TLR4- and MyD88-deficient mice are highly resistant to chronic T. muris infection and develop strong antigen-specific Th2 responses in mucosa-associated lymphoid tissues. Hence, TLR4 and MyD88 are involved not only in the development of pro-inflammatory responses against bacterial pathogens but are also crucially involved in responses against multicellular organisms such as helminths. These results provide the first demonstration of the critical role of TLR4 and MyD88 in bridging the innate and acquired immune response during gastrointestinal nematode infection.
Helmby
Helena
H
School of Biological Sciences, University of Manchester, Manchester, GB.
Grencis
Richard K
RK
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D009349:Nematode Infections / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; D018793:Interleukin-13; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015847:Interleukin-4