首页> 外文期刊>The journal of immunology >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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The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of monocytes and CD4+ T cells during a pulmonary Cryptococcus neoformans infection.

机译:单核细胞趋化蛋白-1(MCP-1)在肺隐球菌感染期间单核细胞和CD4 + T细胞募集中的作用。

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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.
机译:新型隐球菌是通过呼吸道获得的,是艾滋病致死性真菌病的主要原因。 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进入肺的趋化因子。在本研究中,C-C趋化因子单核细胞趋化蛋白-1(MCP-1)的支气管肺泡灌洗液(BAL)水平和炎性细胞的募集在新感染梭状芽孢杆菌的肺部感染后均增加。肺中MCP-1产生的动力学与CD4 + T细胞和单核细胞/巨噬细胞的募集最密切相关。体内中和抗MCP-1 Abs的给药降低了MCP-1的BAL液水平,减少了巨噬细胞(> 95%)和CD4 + T细胞(76 +/- 9%)的募集,并抑制了隐球菌清除率。尽管没有MCP-1的体外嗜中性粒细胞或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有所减少(很可能是减少CD4 + T细胞和巨噬细胞数量的间接作用)。 MCP-1的中和作用还导致TNF-α和IL-6的BAL液水平降低。这是MCP-1在清除感染中的作用的首次证明,并提供了直接的证据表明MCP-1在对新形成梭菌的T细胞依赖性免疫应答中起着关键作用。

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