Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by β-Defensin 2

Author:

Biragyn Arya1,Ruffini Pier Adelchi1,Leifer Cynthia A.2,Klyushnenkova Elena3,Shakhov Alexander3,Chertov Oleg4,Shirakawa Aiko K.5,Farber Joshua M.5,Segal David M.2,Oppenheim Joost J.6,Kwak Larry W.1

Affiliation:

1. Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.

2. Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892-1360, USA.

3. Intramural Research Support Program and

4. Protein Chemistry Laboratory, Science Applications International Corporation, Frederick, MD 21702, USA.

5. Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

6. Laboratory of Molecular Immunoregulation, NCI, Frederick, MD 21702, USA.

Abstract

β-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 β-defensin 2 (mDF2β) 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 mDF2β may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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