期刊
BLOOD
卷 116, 期 18, 页码 3389-3397出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-05-282913
关键词
-
类别
资金
- European Community [EXT 014162]
- Fondation pour la Recherche Medicale (FRM)
- Association pour la Recherche contre le Cancer (ARC)
- Agence National pour la Recherche (ANR)
Microbial infection triggers the endogenous production of immunosuppressive glucocorticoid (GC) hormones and simultaneously activates innate immunity through toll-like receptors (TLRs). How innate immune cells integrate these 2 opposing signals in dictating immunity or tolerance to infection is not known. In this study, we show that human plasmacytoid predendritic cells (pDCs) were highly sensitive to GC-induced apoptosis. Strikingly, they were protected by microbial stimulation through TLR-7 and TLR-9, but not by microbial-independent stimuli, such as interleukin-3, granulocyte macrophage colony-stimulating factor, or CD40-ligand. This protection was dependent on TLR-induced autocrine tumor necrosis factor-alpha and interferon-alpha, which collectively increased the expression ratio between antiapoptotic genes (Bcl-2, Bcl-xL, BIRC3, CFLAR) versus proapoptotic genes (Caspase-8, BID, BAD, BAX). In particular, virus-induced Bcl-2 up-regulation was dependent on autocrine interferon-alpha. Using small interfering RNA technology, we demonstrated that Bcl-2 and CFLAR/c-flip were essential for TLR-induced protection of pDCs from GC-induced caspase-8-mediated apoptosis. Our results demonstrate a novel property of the TLR pathway in regulating the interface between GC and innate immunity and reveal a previously undescribed mechanism of GC resistance. (Blood. 2010; 116(18):3389-3397)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据