LPS, dsRNA and the interferon bridge to adaptive immune responses: Trif, Tram, and other TIR adaptor proteins.
Toll-like receptors (TLRs) expressed on antigen-presenting cells (APCs), form a critical link between innate and the adaptive immune responses. Activation of TLRs by LPS and dsRNA results in up-regulation of co-stimulatory molecules (UCM) essential for the generation of robust T-cell responses. It is now evident that type I interferons (IFNs) play an important role in UCM and in the subsequent maturation of APCs. The recently identified adaptor molecules Trif and Tram, unlike their counterparts MyD88 and MAL/Tirap, induce type I IFN via the TLR4 signaling pathway, whereas Trif appears to be the sole adaptor molecule involved in TLR3 signaling, resulting in subsequent production of type I IFN. Here, we discuss how Trif and type I IFN are involved in the optimization of APC-T cell interaction in response not only to viral but also bacterial stimuli.
Hoebe
Kasper
K
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA. khoebe@scripps.edu
Beutler
Bruce
B
D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology*; D000818:Animals; D006801:Humans; D007372:Interferons / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D012330:RNA, Double-Stranded / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D033942:Adaptor Proteins, Vesicular Transport; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C470409:TICAM1 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D007372:Interferons