Human Toll-like receptor 2 mediates induction of the antimicrobial peptidehuman beta-defensin 2 in response to bacterial lipoprotein

Recognition of pathogens by Drosophila Toll or human Toll-like receptors re sults in translocation of Dorsal or its human homologue NF-HB, respectively ; in Drosophila, this is followed by the production of antimicrobial peptid es serving as antimicrobial effector system of the innate immune response. We investigated whether human Toll-like receptors also mediate induction of the synthesis of antimicrobial peptides. We found that HEK293 cells transf ected with Toll-like receptor 2, but not wild-type cells responded to stimu lation with bacterial lipoprotein by production of human beta-defensin 2. F urthermore, the human lung epithelial cell line A549 was found to constitut ively express Toll-like receptor 2 and to produce beta-defensin 2 in respon se to bacterial lipoprotein. This response was abrogated by blocking the si gnaling pathway activated through Toll-like receptors by transfecting the A 549 cells with a dominant-negative form of IRAK-2. Thus, exposure of human cells to bacterial lipoprotein elicits production of the antimicrobial pept ide beta-defensin 2 through Toll-like receptor 2.