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