Human Toll-like receptor 2 mediates induction of the antimicrobial peptide human beta-defensin 2 in response to bacterial lipoprotein.
Recognition of pathogens by Drosophila Toll or human Toll-like receptors results in translocation of Dorsal or its human homologue NF-kappaB, 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.
Birchler
T
T
Division of Immunology, Hematology, Oncology, Infectiology, Zurich University Children's Hospital, Zurich, Switzerland.
Seibl
R
R
Büchner
K
K
Loeliger
S
S
Seger
R
R
Hossle
J P
JP
Aguzzi
A
A
Lauener
R P
RP
D001426:Bacterial Proteins / Q000494:pharmacology*; D002460:Cell Line; D029721:Drosophila Proteins; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D008074:Lipoproteins / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014158:Transcription, Genetic; D023083:beta-Defensins / Q000096:biosynthesis*
D001426:Bacterial Proteins; C106641:DEFB4A protein, human; D029721:Drosophila Proteins; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D023083:beta-Defensins; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases