Mycobacterial trehalose 6,6′-dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 protein
Mycobacterial trehalose 6,6′-dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 protein
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DOI：
10.1016/j.micpath.2005.03.003
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发表时间：
2005-07-01
影响因子：
3.8
通讯作者：
Kobayashi, K
中科院分区：
文献类型：
--
作者：
Oiso, R;Fujiwara, N;Kobayashi, K
结核分枝杆菌是一种胞内致病菌，其致病性与其逃避巨噬细胞杀伤并诱导迟发型超敏反应（DTH）有关。是M.细胞壁的主要成分。结核病的病原体是海藻糖6，6 '-二霉菌酸酯（TDM），其被认为是致病因子。DTH和细胞免疫的表达依赖于巨噬细胞-细胞因子-1型辅助性T（Th 1）淋巴细胞轴。细胞因子白细胞介素-12（IL-12）和干扰素-γ（IFN-γ）在该过程中起关键作用，并且IL-12激活的信号转导子和转录激活子（STAT）4对于全功能Th 1细胞的发育是必需的。为了阐明宿主对分枝杆菌TDM的反应，我们分析了使用STAT 4缺陷小鼠的实验性肉芽肿病变的足垫反应、组织病理学和细胞因子谱。在本研究中，我们已经证明，分枝杆菌TDM选择性地诱导Th 1反应通过STAT 4信号通路，因为小鼠缺乏STAT 4蛋白显着减少发展DTH，过敏性肉芽肿，和Th 1细胞因子反应，当与BALB/c小鼠相比。这些结果揭示了分枝杆菌病的分子发病机制。结合以往的研究，TDM是一种针对宿主的多效性分子，参与了致病过程。(C)2005爱思唯尔有限公司保留所有权利。
Mycobacterium tuberculosis is an intracellular pathogen of tuberculosis and its pathogenicity is related to the ability to escape killing by ingested macrophages and induce delayed-type hypersensitivity (DTH). A major component of the cell wall of M. tuberculosis is trehalose 6,6'-dimycolate (TDM), which has been implicated as a pathogenetic factor. The expression of DTH and cell-mediated immunity is dependent on the macrophage-cytokine-type 1 helper T (Th1) lymphocyte axis. Cytokines, interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), play a critical role in the process and IL-12-activated signal transducer and activator of transcription (STAT) 4 is required for the development of fully functional Th1 cells. To clarify host responses to mycobacterial TDM, we have analyzed footpad reaction, histopathology and cytokine profile of experimental granulomatous lesions using STAT4-deficient mice. In the present study, we have demonstrated that mycobacterial TDM selectively induces the Th1 response through the STAT4 signaling pathway, because mice lacking STAT4 protein significantly reduced to develop DTH, hypersensitivity granulomas, and Th1 cytokine responses, when compared to BALB/c mice. These results shed light on the molecular pathogenesis of mycobacterial disease. Taken together with previous studies, TDM is a pleiotropic molecule against the host and participates in the pathogenesis. (C) 2005 Elsevier Ltd. All rights reserved.