期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 83, 期 4, 页码 998-1008出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.1007700
关键词
antimicrobial peptide; DC maturation; immunomodulation
资金
- Intramural NIH HHS [Z01 AG000770-04] Funding Source: Medline
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 (mDF2 beta) 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-kappa B- and TNF-alpha-dependent process that does not require TNFR1. We demonstrate that mDF2 beta 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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