The Complement System Facilitates Clearance of Enterococcus faecium during Murine Peritonitis
The Complement System Facilitates Clearance of Enterococcus faecium during Murine Peritonitis
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DOI：
10.1086/650341
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发表时间：
2010-02-15
影响因子：
6.4
通讯作者：
van der Poll, Tom
中科院分区：
文献类型：
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作者：
Leendertse, Masja;Willems, Rob J. L.;van der Poll, Tom
背景。耐多药肠球菌感染是世界范围内一个日益严重的问题。关于宿主对肠球菌疾病的防御知之甚少。体外研究表明，补体蛋白在嗜中性粒细胞介导的吞噬中起着重要作用。在本研究中，我们探讨了补体在粪肠球菌腹膜炎体内模型中的重要性。外周中性粒细胞和腹腔巨噬细胞与失补充或正常血浆预孵育的粪肠杆菌一起孵育，观察吞噬和杀伤情况。用眼镜蛇毒因子（CVF）腹腔注射补体缺乏的C57BL/6小鼠和补体3 （C3）敲除小鼠诱导粪肠杆菌性腹膜炎。分别与生理盐水对照组和野生型小鼠在感染后48 h的几个时间点的感染过程进行比较。补体活化增强了中性粒细胞和巨噬细胞的吞噬作用。cvf处理和C3敲除小鼠在清除研究的所有器官和组织（腹膜液、血液、肺和肝脏）中的屎肠杆菌方面受到严重阻碍。失补体小鼠腹膜细胞因子和趋化因子水平升高，而全身或腹膜细胞动力学未见差异。补体缺乏严重阻碍粪肠杆菌腹膜炎和随后的全身感染的清除。
Background. Infections with multidrug-resistant enterococci are a growing problem worldwide. Little is known about the host defense against enterococcal diseases. In vitro studies have demonstrated an important role played by complement proteins in neutrophil-mediated phagocytosis. In this study, we investigated the importance of complement in an in vivo model of Enterococcus faecium peritonitis.Methods. Peripheral neutrophils and peritoneal macrophages were incubated with E. faecium that had been preincubated with decomplemented or normal plasma, and phagocytosis and killing were examined. E. faecium peritonitis was induced in C57BL/6 mice rendered complement deficient by intraperitoneal injection with cobra venom factor (CVF) and in complement 3 (C3) knockout mice. The course of the infection was compared with that in saline control and wild-type mice, respectively, at several time points up to 48 h after infection.Results. Opsonization by complement enhanced phagocytosis by neutrophils and macrophages. CVF-treated and C3 knockout mice were severely hampered in clearing E. faecium from all organs and tissues under study (peritoneal fluid, blood, lungs, and liver). Higher peritoneal cytokine and chemokine levels were measured in decomplemented mice, whereas no differences in systemic or peritoneal cell kinetics were detected.Conclusion. Complement deficiency severely hampers the clearance of E. faecium peritonitis and subsequent systemic infection.