The class A scavenger receptor, macrophage receptor with collagenous structure, is the major phagocytic receptor for Clostridium sordellii expressed by human decidual macrophages.
The class A scavenger receptor, macrophage receptor with collagenous structure, is the major phagocytic receptor for Clostridium sordellii expressed by human decidual macrophages.
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DOI：
10.4049/jimmunol.1000989
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发表时间：
2010-10-01
期刊：
影响因子：
--
通讯作者：
Aronoff DM
中科院分区：
文献类型：
--
作者：
Thelen T;Hao Y;Medeiros AI;Curtis JL;Serezani CH;Kobzik L;Harris LH;Aronoff DM
索氏梭状芽胞杆菌是一种新出现的病原体，与分娩、流产或宫颈器械术后高度致命的女性生殖道感染有关。我们对索氏弧菌感染发病机制的认识存在差距，这对针对这一问题制定更好的预防和治疗策略构成了重大挑战。我们试图确定子宫蜕膜巨噬细胞吞噬这种细菌的机制，并检验了人类蜕膜巨噬细胞利用A类清道夫受体(CaSR)内化未调理的索氏杆菌的假设。体外培养的人蜕膜巨噬细胞与CASRs的药物抑制剂(岩藻糖胶、多聚肌苷酸和葡聚糖硫酸盐)孵育后进行的吞噬试验表明，这些受体在索氏锥虫的吞噬作用中发挥了作用。可溶性MARCO受体可阻止沙门氏菌内化，提示MARCO是该菌蜕膜巨噬细胞吞噬过程中的重要CaSR。来自Marco基因缺陷小鼠的腹膜巨噬细胞，而不是野生型或SR-AI/II基因缺陷小鼠，显示出索氏弧菌吞噬功能受损。Marco零基因小鼠比野生型小鼠更容易死于索氏锥虫子宫感染，并表现出这种细菌从受感染的子宫中清除的障碍。因此，Marco是一种重要的吞噬细胞受体，被人和小鼠巨噬细胞用来清除感染子宫中的索氏杆菌。
Clostridium sordellii is an emerging pathogen associated with highly-lethal female reproductive tract infections following childbirth, abortion, or cervical instrumentation. Gaps in our understanding of the pathogenesis of C. sordellii infections present major challenges to the development of better preventive and therapeutic strategies against this problem. We sought to determine the mechanisms whereby uterine decidual macrophages phagocytose this bacterium and tested the hypothesis that human decidual macrophages utilize class A scavenger receptors (CASR) to internalize unopsonized C. sordellii. In vitro phagocytosis assays with human decidual macrophages incubated with pharmacological inhibitors of CASRs (fucoidan, polyinosinic acid, and dextran sulfate) revealed a role for these receptors in C. sordellii phagocytosis. Soluble MARCO receptor prevented C. sordellii internalization, suggesting that MARCO is an important CASR in decidual macrophage phagocytosis of this microbe. Peritoneal macrophages from MARCO-deficient mice, but not wild-type or SR-AI/II-deficient mice, showed impaired C. sordellii phagocytosis. MARCO-null mice were more susceptible to death from C. sordellii uterine infection than wild-type mice and exhibited impaired clearance of this bacterium from the infected uterus. Thus, MARCO is an important phagocytic receptor utilized by human and mouse macrophages to clear C. sordellii from the infected uterus.
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