Mycobacterial glycolipid trehalose 6,6′-dimycolate-induced hypersensitive granulomas:: contribution of CD4+ lymphocytes
Mycobacterial glycolipid trehalose 6,6′-dimycolate-induced hypersensitive granulomas:: contribution of CD4+ lymphocytes
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DOI：
10.1099/mic.0.2007/010850-0
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发表时间：
2007-10-01
期刊：
影响因子：
2.8
通讯作者：
Actor, Jeffrey K.
中科院分区：
文献类型：
--
作者：
Guidry, Tera V.;Hunter, Robert L., Jr.;Actor, Jeffrey K.
肉芽肿反应是结核分枝杆菌感染的一个特征性组织学特征，负责生物遏制。细胞介导的免疫的发展对于预防疾病是必不可少的，也是维持隔离性肉芽肿反应所必需的。海藻糖6，6 '-二霉菌酸酯（TDM;索因子）是一种与分枝杆菌细胞壁相关的糖脂，被认为是分枝杆菌中的关键免疫原性组分。肺结核感染。TDM诱导的过敏性肉芽肿反应模型具有与活动性结核感染相似的病理学。用TDM对小鼠进行预先免疫（致敏）导致在随后的TDM攻击后加重的组织学损伤、炎症和淋巴细胞浸润。进行连续转移实验以确定控制这种反应的细胞表型; CD 4（+）细胞被鉴定为相关病理学发展的关键。接受来自供体TDM免疫小鼠的CD 4（+）细胞的小鼠在随后的TDM攻击后表现出显著增加的Th 1型细胞因子IFN-γ和IL-12在肺内的产生。接受初始CD 4（+）细胞或从TDM免疫供体分离的CD 8（+）或CD 19（+）细胞的对照组未表现出加重的应答。从TDM免疫的小鼠中分离的鉴定的CD 4（+）细胞在体外暴露于TDM脉冲的巨噬细胞时产生显著量的IFN-γ和IL-2。这些实验提供了进一步的证据，表明TDM诱导的肉芽肿形成中涉及细胞介导的反应，其模拟了M.肺结核感染。
The granulomatous response is a characteristic histological feature of Mycobacterium tuberculosis infection responsible for organism containment. The development of cell-mediated immunity is essential for protection against disease, as well as being required for maintenance of the sequestering granulomatous response. Trehalose 6,6'-dimycolate (TDM; cord factor), a glycolipid associated with the cell wall of mycobacteria, is implicated as a key immunogenic component in M. tuberculosis infection. Models of TDM-induced hypersensitive granulomatous response have similar pathologies to that of active tuberculosis infection. Prior immunization (sensitization) of mice with TDM results in exacerbated histological damage, inflammation and lymphocytic infiltration upon subsequent TDM challenge. Adoptive transfer experiments were performed to ascertain the cell phenotype governing this response; CD4(+) cells were identified as critical for development of related pathology. Mice receiving CD4(+) cells from donor TDM-immunized mice demonstrated significantly increased production of Th 1-type cytokines IFN-gamma and IL-12 within the lung upon subsequent TDM challenge. Control groups receiving naive CD4(+) cells, or CD8(+) or CD19(+) cells isolated from TDM-immunized donors, did not exhibit an exacerbated response. The identified CD4(+) cells isolated from TDM-immunized mice produced significant amounts of IFN-gamma and IL-2 when exposed to TDM-pulsed macrophages in vitro. These experiments provide further evidence for involvement of a cell-mediated response in TDM-induced granuloma formation, which mimics pathological damage elicited during M. tuberculosis infection.