References
Query Results -- Details
MGI Accession ID: MGI:3785117
J Number: J:134193
Other Accession IDs:
Title: Murine beta-defensin 2 promotes TLR-4/MyD88-mediated and NF-kappaB-dependent atypical death of APCs via activation of TNFR2.
Authors: Biragyn A; Coscia M; Nagashima K; Sanford M; Young HA; Olkhanud P
Journal: J Leukoc Biol
Volume: 83
Issue: 4
Date: 2008 Apr
Year: 2008
Pages: 998-1008
Review Status: Peer Reviewed
Abstract:
Mammalian antimicrobial peptides, including beta-defensins, represent an ancient arm of innate immunity designed to directly neutralize invading microbes. Previously, we demonstrated that murine beta-defensin 2 (mDF2beta) also acted as an endogenous ligand for TLR-4-activating maturation of dendritic cells (DCs). Herein, we report that this TLR-4 -dependent activation leads to induction of an atypical cell death that is unexpectedly exaggerated by the inhibition of caspases. Experiments using APCs with nonfunctional TNF-alpha or its receptors suggest that this is a NF-kappaB- and TNF-alpha-dependent process that does not require TNFR1. We demonstrate that mDF2beta triggers a TNFR2-mediated signaling cascade of 'self-destruction' through up-regulation of membrane-bound TNF-alpha and TNFR2. This appears not to be an isolated phenomenon, as human synthetic beta-defenisn 3 was also able to activate and kill DCs. We propose that beta-defenins may play an important immunoregulatory role as controllers of the natural process of elimination of activated APCs.
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