Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation
Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation
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DOI：
10.1189/jlb.0406294
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发表时间：
2006-10-01
影响因子：
5.5
通讯作者：
Re, Fabio
中科院分区：
文献类型：
--
作者：
Li, Hanfen;Nookala, Suba;Re, Fabio
土拉热弗朗西丝菌是一种革兰氏阴性兼性胞内细菌，是土拉菌病的病原体，也是A类生物恐怖剂。兔热病的发病机制目前还知之甚少。本文描述了F.土拉菌感染先天免疫系统我们已经发现，在人类和小鼠树突状细胞中，F。土拉热引起以产生大量细胞因子和趋化因子为特征的强有力的炎症反应。使用来源于TLR 2缺陷的细胞。小鼠和体外转染试验，我们证明了这种反应是由TLR 2介导的，不需要LPS结合蛋白。F.土拉热似乎激活了TLR 2/TLR 1和TLR 2/TLR 6异二聚体。IL-1 β的分泌是半胱天冬酶-1激活的反映，由活的而不是热灭活的F诱导。土拉热菌，尽管事实上这两种形式的细菌同样诱导IL-1 β转录。我们的研究结果表明，TLR 2和caspase-1的激活是两个主要的细胞通路负责炎症反应的F。土拉热。J. Leukoc. 80：766-773; 2006.
Francisella tularensis, a gram-negative, facultative, intracellular bacterium, is the etiologic agent of tularemia and a category A bioterrorism agent. Little is known about the mechanism of pathogenesis of tularemia. In this paper, we describe the interaction of the live vaccine strain of F. tularensis with the innate immune system. We have found that in human and mouse dendritic cells, F. tularensis elicited a powerful inflammatory response, characterized by production of a number of cytokines and chemokines. Using cells derived from TLR2-deficient. mice and in vitro transfection assays, we demonstrated that this response was mediated by TLR2 and did not require the LPS-binding protein. F. tularensis appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers. IL-1 beta secretion, a reflection of caspase-1 activation, was induced by live but not heat-killed F. tularensis, despite the fact that both forms of the bacterium equally induced the IL-1 beta transcript. Our results identified activation of TLR2 and caspase-1 as the two main cellular pathways responsible for the inflammatory response to F. tularensis. J. Leukoc. Biol. 80: 766-773; 2006.