Role of chemokine ligand 2 in the protective response to early murine pulmonary tuberculosis
Role of chemokine ligand 2 in the protective response to early murine pulmonary tuberculosis
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DOI：
10.1046/j.1365-2567.2003.01680.x
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发表时间：
2003-08-01
期刊：
影响因子：
6.4
通讯作者：
Cooper, AM
中科院分区：
文献类型：
--
作者：
Kipnis, A;Basaraba, RJ;Cooper, AM
趋化因子在结核病免疫的发展中起重要作用。趋化因子配体2（CCL 2，JE，monocyte chemoattractant protein-1）被认为主要负责募集单核细胞、树突状细胞、自然杀伤细胞和活化的T细胞，所有这些细胞在有效控制小鼠结核感染中发挥关键作用。我们在这里表明，在CCL 2基因被破坏的小鼠中，低剂量结核分枝杆菌气溶胶感染导致更少的巨噬细胞进入肺部，但肺部细菌负荷仅轻微和短暂增加;这些小鼠仍然能够建立慢性疾病状态。这些动物表现出与野生型小鼠相似的活化T细胞数量，这通过它们的CD 44（hi）CD 62（lo）表型表达来确定，但分泌干扰素-γ的细胞短暂减少。这些数据表明，小鼠不能产生CCL 2的主要缺陷是暂时未能将抗原特异性T淋巴细胞聚集到感染的肺中，而获得性宿主反应的其他元素通过与趋化因子受体CCR 2相互作用的不同配体来补偿。
Chemokines play an important role in the development of immunity to tuberculosis. Chemokine ligand 2 (CCL2, JE, monocyte chemoattractant protein-1) is thought to be primarily responsible for recruiting monocytes, dendritic cells, natural killer cells and activated T cells, all of which play critical roles in the effective control of tuberculosis infection in mice. We show here that in mice in which the CCL2 gene was disrupted, low-dose aerosol infection with Mycobacterium tuberculosis resulted in fewer macrophages entering the lungs, but only a minor and transient increase in bacterial load in the lungs; these mice were still able to establish a state of chronic disease. Such animals showed similar numbers of activated T cells as wild-type mice, as determined by their expression of the CD44(hi) CD62(lo) phenotype, but a transient reduction in cells secreting interferon-gamma. These data indicate that the primary deficiency in mice unable to produce CCL2 is a transient failure to focus antigen-specific T lymphocytes into the infected lung, whereas other elements of the acquired host response are compensated for by different ligands interacting with the chemokine receptor CCR2.