Macrophages exposed to Mycobacterium tuberculosis release chemokines able to recruit selected leucocyte subpopulations:: focus on γδ cells

Macrophages exposed to Mycobacterium tuberculosis release chemokines able to recruit selected leucocyte subpopulations:: focus on γδ cells
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DOI:
10.1046/j.1365-2567.2003.01600.x
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发表时间:
2003-03-01
期刊:
影响因子:
6.4
通讯作者:
Pardi, R
Pardi, R
中科院分区:
医学2区
文献类型:
--
作者:
Ferrero, E;Biswas, P;Pardi, R

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肉芽肿是结核病的典型特征。我们评估了体外巨噬细胞与结核分枝杆菌(MT)衍生产物孵育诱导的选定人类白细胞亚群的趋化性。单核细胞趋化蛋白1(MCP-1)和白细胞介素8(IL-8)的释放与特异性诱导对单核细胞和多形核白细胞(PMNs)的强趋化性相关。γ δ和辅助性T细胞1型(Th 1)α淋巴细胞的化学吸引,而T-静息,IL-2激活和Th 2淋巴细胞不受影响。活化与分枝杆菌衍生的,含磷酸盐的成分,调节趋化因子受体的γ δ T淋巴细胞以及其模式的细胞趋化因子的生产,揭示了他们的积极参与肉芽肿形成的潜力。特别是,CXCR 3和IP-10,我们发现由MT脉冲肺泡巨噬细胞释放,似乎代表了受体-反受体对参与γ δ淋巴细胞的趋化性。免疫组织化学分析和原位杂交显示,在体内存在的IL-8,MCP-1和IL-10的淋巴结和肺结核肉芽肿。我们的研究结果强调了MT提取物在诱导巨噬细胞源性趋化因子中的作用,这些趋化因子负责协调中性粒细胞、单核细胞、Th 1和γ δ T细胞的募集,以及γ δ功能的调节。
Granuloma is a typical feature of tuberculosis. We evaluated the chemotaxis of selected human leucocyte subsets induced by macrophages incubated with Mycobacterium tuberculosis (MT)-derived products in vitro . The release of monocyte chemotactic protein 1 (MCP-1) and interleukin-8 (IL-8) correlated with the specific induction of strong chemotaxis towards monocytes and polymorphonuclear leucocytes (PMNs). gammadelta and T helper type 1 (Th1) alphabeta lymphocytes were chemoattracted, while T-resting, IL-2-activated and Th2 lymphocytes were unaffected. Activation with mycobacterium-derived, phosphate-containing components, modulated the chemokine receptor profile of gammadelta T lymphocytes as well as their pattern of cyto-chemokine production, disclosing a potential for their active participation in granuloma formation. In particular, CXCR3 and IP-10, which we found to be released by MT-pulsed alveolar macrophages, seem to represent the receptor-counter-receptor pair implicated in the chemotaxis of gammadelta lymphocytes. Immunohistochemical analysis and in situ hybridization revealed the in vivo presence of IL-8, MCP-1 and IL-10 in lymph node and lung tuberculous granulomas. Our results underscore the role of MT extracts in the induction of macrophage-derived chemokines responsible for the orchestrated recruitment of PMNs, monocytes, and Th1 and gammadelta T cells, as well as in the regulation of gammadelta function.