title: Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2.
abstract: There is increasing evidence that innate and adaptive immune responses are intimately linked. This linkage is in part mediated through the recognition of conserved microbial products by Toll-like receptors (TLRs). Detection of microbial products by TLRs can result in induction of inflammatory cytokines and activation of professional antigen-presenting cells, thereby enhancing adaptive immune responses. Here, we show that human beta-defensin-3 (hBD-3), an innate antimicrobial peptide, can induce expression of the costimulatory molecules CD80, CD86, and CD40, on monocytes and myeloid dendritic cells in a TLR-dependent manner. Activation of monocytes by hBD-3 is mediated by interaction with TLRs 1 and 2, resulting in signaling that requires myeloid differentiating factor 88 and results in IL-1 receptor-associated kinase-1 phosphorylation. In studies with HEK cells engineered to express various TLRs, we show that activation of NF-kappaB by hBD-3 depends on the expression of both TLR1 and TLR2. Thus, human TLR signaling is not restricted to recognition of microbial patterns but also can be initiated by host-derived peptides such as hBD-3.
authors.affiliation: Departments of Molecular Biology and Microbiology and Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Funderburg
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Feng
authors.forename: Michael G
authors.initials: MG
authors.lastname: Drage
authors.forename: Julie
authors.initials: J
authors.lastname: Jadlowsky
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
authors.forename: Aaron
authors.initials: A
authors.lastname: Weinberg
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
mesh_terms: D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051194:Toll-Like Receptor 1 / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D023083:beta-Defensins / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; C422950:DEFB103A protein, human; D053594:Myeloid Differentiation Factor 88; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D023083:beta-Defensins; D053592:Interleukin-1 Receptor-Associated Kinases