Maturation modulates caspase-1-independent responses of dendritic cells to Anthrax lethal toxin.
Maturation modulates caspase-1-independent responses of dendritic cells to Anthrax lethal toxin.
复制标题
成熟调节树突状细胞对炭疽致命毒素的独立于 caspase-1 的反应。
DOI：
10.1111/j.1462-5822.2008.01121.x
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发表时间：
2008
影响因子：
3.4
通讯作者：
vanderGoot,FGisou
中科院分区：
文献类型：
--
作者：
Reig,Núria;Jiang,Aimin;Couture,Rachael;Sutterwala,FayyazS;Ogura,Yasunori;Flavell,RichardA;Mellman,Ira;vanderGoot,FGisou
炭疽致死毒素（Anthrax lethal toxin，LT）通过损害巨噬细胞和树突状细胞（dendritic cells，DCs）等免疫系统细胞的功能，参与炭疽杆菌的免疫逃避策略。来自某些近交系小鼠品系的巨噬细胞在LT处理后通过依赖于Nalp 1b（一种炎性体组分）的半胱天冬酶-1活化介导快速死亡。然而，在人和许多小鼠品系的巨噬细胞中未观察到快速LT诱导的死亡。在这里，我们专注于各种小鼠DC对LT的反应。使用各种基因敲除小鼠，我们发现，根据小鼠品系，骨髓来源的DC和巨噬细胞的死亡是由快速Nalp 1b和caspase-1依赖性介导的，或者由MEK 1/2通路受损触发的缓慢caspase-1独立通路介导的。在不同遗传背景的细胞中观察到Caspase-1非依赖性死亡，有趣的是仅发生在未成熟DC中。不同类型的刺激触发的成熟导致DC的完全保护。这些研究表明，LT造成的细胞损伤不仅取决于先天反应，还取决于细胞的成熟阶段，这调节了更普遍的caspase-1非依赖性反应。
Anthrax lethal toxin (LT) contributes to the immune evasion strategy ofBacillus anthracisby impairing the function of cells of the immune system, such as macrophages and dendritic cells (DCs). Macrophages from certain inbred mice strains undergo rapid death upon LT treatment mediated by caspase‐1 activation dependent on Nalp1b, an inflammasome component. Rapid LT‐induced death is however, not observed in macrophages from human and many mouse strains. Here, we focused on the responses of various murine DCs to LT. Using a variety of knockout mice, we found that depending on the mouse strain, death of bone marrow‐derived DCs and macrophages was mediated either by a fast Nalp1b and caspase‐1‐dependent, or by a slow caspase‐1‐independent pathway that was triggered by the impairment of MEK1/2 pathways. Caspase‐1‐independent death was observed in cells of different genetic backgrounds and interestingly occurred only in immature DCs. Maturation, triggered by different types of stimuli, led to full protection of DCs. These studies illustrate that the cellular damage inflicted by LT depends not only on the innate responses but also on the maturation stage of the cell, which modulates the more general caspase‐1‐independent responses.