Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2.
beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.
Biragyn
Arya
A
Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. arya@mail.ncifcrf.gov
Ruffini
Pier Adelchi
PA
Leifer
Cynthia A
CA
Klyushnenkova
Elena
E
Shakhov
Alexander
A
Chertov
Oleg
O
Shirakawa
Aiko K
AK
Farber
Joshua M
JM
Segal
David M
DM
Oppenheim
Joost J
JJ
Kwak
Larry W
LW
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D054399:Receptors, CCR6; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D019707:Receptors, Chemokine / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014162:Transfection; D023083:beta-Defensins / Q000494:pharmacology / Q000502:physiology*
D000951:Antigens, Neoplasm; C106311:CCR6 protein, human; D019496:Cancer Vaccines; D016207:Cytokines; C106641:DEFB4A protein, human; D029721:Drosophila Proteins; D016898:Interferon-alpha; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D054399:Receptors, CCR6; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D023083:beta-Defensins