title: Crosstalk between complement and toll-like receptors.
abstract: The complement system and toll-like receptors (TLRs) are two components of innate immunity that are critical for first-line host defense. Many pathogen-associated molecular patterns activate both complement and TLRs, and recent studies in animal models have revealed a marked synergistic interaction between the two systems. In mice deficient in a membrane complement regulator, prototypical TLR ligands such as LPS, zymosan, and polyI:C caused increased systemic complement activation, which in turn led to a profound elevation of proinflammatory cytokine biosynthesis. This phenotype required interaction between complement and TLRs because complement activation alone by cobra venom factor without TLR engagement did not lead to appreciable cytokine production. The regulatory effect of complement on TLR signaling was mediated by the anaphylatoxins C5a and C3a through a receptor-dependent mechanism and involved increased mitogen-activated protein kinase and nuclear factor κB activation. The crosstalk between complement and TLRs may also impact adaptive immunity, for example, the differentiation of T helper 17 (Th-17) cells. Given that excessive activation of either TLR or complement has been associated with inflammatory tissue injury as occurs in sepsis and autoimmune diseases, the new insight on complement and TLR crosstalk may have therapeutic implications.
authors: Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. songwe@upenn.edu
authors: Wen-Chao
authors: WC
authors: Song
mesh_terms: D000818:Animals; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D020239:Receptor Cross-Talk / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
chemical_list: D051193:Toll-Like Receptors; D003165:Complement System Proteins