Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2.

TitleHuman -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2.
Publication TypeJournal Article
Year of Publication2007
AuthorsFunderburg N, Lederman MM, Feng Z, Drage MG, Jadlowsky J, Harding CV, Weinberg A, Sieg SF
JournalProc Natl Acad Sci U S A
Volume104
Issue47
Pagination18631-5
Date Published2007 Nov 20
ISSN1091-6490
KeywordsAntigen-Presenting Cells, Antigens, CD, beta-Defensins, Cells, Cultured, Humans, Interleukin-1 Receptor-Associated Kinases, Monocytes, Myeloid Differentiation Factor 88, Phosphorylation, Signal Transduction, Toll-Like Receptor 1, Toll-Like Receptor 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.

DOI10.1073/pnas.0702130104
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID18006661
PubMed Central IDPMC2141828
Grant ListR01DE017335 / DE / NIDCR NIH HHS / United States
R01DE15510 / DE / NIDCR NIH HHS / United States