The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of monocytes and CD4+ T cells during a pulmonary Cryptococcus neoformans infection.
The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of monocytes and CD4+ T cells during a pulmonary Cryptococcus neoformans infection.
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DOI：
10.4049/jimmunol.155.10.4790
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发表时间：
1995-11
影响因子：
4.4
通讯作者：
G. Huffnagle;R. Strieter;T. Standiford;R. McDonald;M. Burdick;S. Kunkel;G. Toews
中科院分区：
文献类型：
--
作者：
G. Huffnagle;R. Strieter;T. Standiford;R. McDonald;M. Burdick;S. Kunkel;G. Toews
新型隐球菌是通过呼吸道获得的，是艾滋病致命真菌病的主要原因。T细胞介导的肺部炎症反应的发展对于清除这种病原体至关重要;然而，尚未确定介导炎性细胞募集到肺部的趋化因子。在本研究中，支气管肺泡灌洗液（BAL）中C-C趋化因子单核细胞趋化蛋白-1（MCP-1）的水平和炎症细胞的募集均在肺部感染后增加。新人类肺中MCP-1产生的动力学与CD 4 + T细胞和单核细胞/巨噬细胞的募集最密切相关。体内施用中和性抗MCP-1抗体降低了MCP-1的BAL液水平，减少了巨噬细胞（> 95%）和CD 4 + T细胞（76 +/- 9%）的募集，并抑制了隐球菌的清除。尽管没有关于MCP-1的体外中性粒细胞或B细胞趋化活性的报道，但在抗MCP-1处理的小鼠中这些白细胞的募集也减少了（最可能是减少CD 4 + T细胞和巨噬细胞数量的间接效应）。MCP-1的中和也导致BAL液中TNF-α和IL-6水平降低。这是第一次证明MCP-1在清除感染中的作用，并提供了直接证据表明MCP-1在T细胞依赖性免疫应答中起关键作用。新人类
Cryptococcus neoformans is acquired via the respiratory tract and is the leading cause of fatal mycosis in AIDS. Development of a T cell-mediated pulmonary inflammatory response is critical for clearance of this pathogen; however, the chemotactic factors that mediate inflammatory cell recruitment into the lungs have not been identified. In the present study, the bronchoalveolar lavage (BAL) fluid levels of the C-C chemokine monocyte chemotactic protein-1 (MCP-1) and the recruitment of inflammatory cells both increased following pulmonary infection with C. neoformans. The kinetics of MCP-1 production in the lungs correlated most closely with the recruitment of CD4+ T cells and monocytes/macrophages. Administration of neutralizing anti-MCP-1 Abs in vivo reduced the BAL fluid levels of MCP-1, decreased the recruitment of both macrophages (> 95%) and CD4+ T cells (76 +/- 9%), and inhibited cryptococcal clearance. Although no in vitro neutrophil or B cell chemotactic activity has been reported for MCP-1, recruitment of these leukocytes was also decreased in anti-MCP-1-treated mice (most likely an indirect effect of reducing the number of CD4+ T cells and macrophages). Neutralization of MCP-1 also resulted in decreased BAL fluid levels of TNF-alpha and IL-6. This is the first demonstration of a role for MCP-1 in clearance of an infection, and provides direct evidence that MCP-1 plays a critical role in the T cell-dependent immune response to C. neoformans.