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Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by -Defensin 2
Arya Biragyn,1*Pier Adelchi Ruffini,1Cynthia A. Leifer,2Elena Klyushnenkova,3Alexander Shakhov,3Oleg Chertov,4Aiko K. Shirakawa,5Joshua M. Farber,5David M. Segal,2Joost J. Oppenheim,6Larry W. Kwak1
-Defensins are small antimicrobial peptides of
the innate immune system produced in response to microbial infection of
mucosaltissue and skin. We demonstrate that murine -defensin 2 (mDF2)acts directly on immature dendritic cells as an endogenous
ligandfor Toll-like receptor 4 (TLR-4), inducing up-regulation
of costimulatorymolecules and dendritic cell maturation. These events,
in turn,trigger robust, type 1 polarized adaptive immune responses invivo, suggesting that mDF2 may play an important role in
immunosurveillanceagainst pathogens and, possibly, self antigens or
tumor antigens.
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.
*
To whom correspondence should be addressed. E-mail:
arya{at}mail.ncifcrf.gov
On leave of absence from Divisione di Oncologia Medica
Falck, Ospedale Niguarda Ca Granda, Milan, Italy.
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44, 3795-3801
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Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: Activation of Toll-like receptor 7.
J. Lee, T.-H. Chuang, V. Redecke, L. She, P. M. Pitha, D. A. Carson, E. Raz, and H. B. Cottam (2003)
PNAS
100, 6646-6651
|Abstract »|Full Text »|PDF »
-Defensin 2
-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 
