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

Abstract
Recognition of pathogens by Drosophila Toll or human Toll‐like receptors results in translocation of Dorsal or its human homologue NF‐κB, respectively; in Drosophila, this is followed by the production of antimicrobial peptides 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 transfected with Toll‐like receptor 2, but not wild‐type cells responded to stimulation with bacterial lipoprotein by production of human beta‐defensin 2. Furthermore, the human lung epithelial cell line A549 was found to constitutively express Toll‐like receptor 2 and to produce beta‐defensin 2 in response to bacterial lipoprotein. This response was abrogated by blocking the signaling pathway activated through Toll‐like receptors by transfecting the A549 cells with a dominant‐negative form of IRAK‐2. Thus, exposure of human cells to bacterial lipoprotein elicits production of the antimicrobial peptide beta‐defensin 2 through Toll‐like receptor 2.