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PMID: 12411706 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2.

Science (New York, N.Y.) ·Vol. 298 ·No. 5595 ·2002-11-01 ·Pages 1025-9

Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW

Abstract

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.

MeSH Terms
Animals Antigens, Neoplasm/immunology Cancer Vaccines/immunology Cell Line Cytokines/biosynthesis Dendritic Cells/immunology Drosophila Proteins Female Humans Interferon-alpha/physiology Ligands Lipopolysaccharides/immunology,pharmacology Lymphocyte Culture Test, Mixed Membrane Glycoproteins/genetics,physiology Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Neoplasms/immunology,therapy Receptors, CCR6 Receptors, Cell Surface/genetics,physiology Receptors, Chemokine/metabolism Recombinant Fusion Proteins/pharmacology Signal Transduction Toll-Like Receptor 4 Toll-Like Receptors Transfection beta-Defensins/pharmacology,physiology
Chemicals
Antigens, Neoplasm CCR6 protein, human Cancer Vaccines Cytokines DEFB4A protein, human Drosophila Proteins Interferon-alpha Ligands Lipopolysaccharides Membrane Glycoproteins Receptors, CCR6 Receptors, Cell Surface Receptors, Chemokine Recombinant Fusion Proteins TLR4 protein, human Toll-Like Receptor 4 Toll-Like Receptors beta-Defensins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Biragyn Arya
Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. [email protected]
Ruffini Pier Adelchi
Leifer Cynthia A
Klyushnenkova Elena
Shakhov Alexander
Chertov Oleg
Shirakawa Aiko K
Farber Joshua M
Segal David M
Oppenheim Joost J
Kwak Larry W
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2002-11-01
Pages
1025-9
Language
English
Region
United States
NLM ID
0404511
Subset
IM
Grants
NCI NIH HHS · N0L-CO-12400 · United States
Corrections
CommentIn
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