| First Author | Biragyn A | Year | 2008 |
| Journal | J Leukoc Biol | Volume | 83 |
| Issue | 4 | Pages | 998-1008 |
| PubMed ID | 18192488 | Mgi Jnum | J:134193 |
| Mgi Id | MGI:3785117 | Doi | 10.1189/jlb.1007700 |
| Citation | Biragyn A, et al. (2008) Murine beta-defensin 2 promotes TLR-4/MyD88-mediated and NF-kappaB-dependent atypical death of APCs via activation of TNFR2. J Leukoc Biol 83(4):998-1008 |
| abstractText | 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. |
