Chemokine receptor 5 and its ligands in the immune response to murine tuberculosis
Chemokine receptor 5 and its ligands in the immune response to murine tuberculosis
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DOI：
10.1016/j.tube.2004.10.003
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发表时间：
2005-05-01
期刊：
影响因子：
3.2
通讯作者：
Mason, CM
中科院分区：
文献类型：
--
作者：
Badewa, AP;Quinton, LJ;Mason, CM
背景：趋化因子，如巨噬细胞炎症蛋白 (MIP)-1 α、MIP-1 β 和激活调节、正常 T 细胞表达和分泌 (RANTES) 吸引和激活 T 细胞和单核细胞（肉芽肿的组成部分）的能力表明，这些趋化因子可能在调节结核分枝杆菌感染的免疫反应中发挥作用。 目的：我们假设趋化因子受体 5 (CCR5) 配体 MIP-1 α、MIP-1 β 和 RANTES 与结核分枝杆菌感染的毒力相关，并且是肉芽肿形成所不可缺少的。 设计：在蛋白质和 mRNA 水平上确定结核分枝杆菌的强毒力 (H37Rv) 和无毒力 (H37Ra) 菌株在体内和体外诱导趋化因子产生的能力。我们还比较了细菌。 H37Rv 感染的 CCR5-/- 或野生型 C57BL/6 小鼠中的负荷、肉芽肿数量和大小。结果：在体内，MIP-1 α、MIP-1 β 和 RANTES 的肺 mRNA 和蛋白测量表明，H37Rv 感染的小鼠的值（第 14-28 天）显着高于 H37Ra 感染的小鼠（p < 0.05）。这与毒力菌株较高的感染负担是一致的。然而，H37Rv 或 H37Ra 的体外肺泡巨噬细胞刺激在所有时间点上三种趋化因子的产生均未产生显着差异。与野生型小鼠相比，肉芽肿的组织学分析未显示 CCR5-/- 中的肉芽肿数量、大小和结核分枝杆菌生长存在任何显着差异。结论：CCR5 配体、MIP-1 α、MIP-1 β 和 RANTES 的产生与结核分枝杆菌的毒力没有明显相关性。这些配体及其受体对于小鼠结核病肉芽肿的发展可能不是必不可少的。 (c) 2004 Elsevier Ltd. 保留所有权利。
Setting: The ability of chemokines such as macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and regulated-upon-activation, normal T cell expressed and secreted (RANTES), to attract and activate T cells and monocytes, the building blocks of the granuloma, suggests that these chemokines may have a role in modulating immune responses to Mycobacterium tuberculosis infection.Objective: We hypothesized that the chemokine receptor 5 (CCR5) ligands, MIP-1 alpha, MIP-1 beta and RANTES, are virulence correlates in M. tuberculosis infection and are indispensable to granuloma formation.Design: The ability of virulent (H37Rv) and avirulent (H37Ra) strains of M. tuberculosis to induce chemokine production in vivo and in vitro was determined at protein and mRNA levels. We also compared bacterial. burden, and granuloma numbers and size in H37Rv-infected CCR5-/- or wild-type C57BL/6 mice.Results: In vivo, lung mRNA and protein measurements of MIP-1 alpha, MIP-1 beta and RANTES indicate significantly higher (p < 0.05) values (days 14-28) in the H37Rv-infected than the H37Ra-infected mice. This is consistent with a higher infection burden of the virulent strain. However, in vitro alveolar macrophage stimulation by H37Rv or H37Ra yielded no significant differences in production of the three chemokines at all time points. Histological analysis of granulomas did not show any significant differences in granuloma numbers, size and M. tuberculosis growth in CCR5-/- compared to wild-type mice.Conclusions: The production of the CCR5 ligands, MIP-1 alpha, MIP-1 beta, and RANTES, does not clearly correlate with virulence of M. tuberculosis. These ligands and their receptors may not be indispensable to the development of granulomas in murine tuberculosis. (c) 2004 Elsevier Ltd. All rights reserved.