Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam. The Netherlands.
J Infect Dis. 2010 Feb 15;201(4):544-52. doi: 10.1086/650341.
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.
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.
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.
Complement deficiency severely hampers the clearance of E. faecium peritonitis and subsequent systemic infection.
全球范围内，耐多药肠球菌感染是一个日益严重的问题。人们对于抵抗肠球菌病的宿主防御机制知之甚少。体外研究已经证明了补体蛋白在中性粒细胞介导的吞噬作用中发挥着重要作用。在本研究中，我们研究了补体在屎肠球菌腹膜炎的体内模型中的重要性。
用预先用去补体或正常血浆孵育的屎肠球菌孵育外周血中性粒细胞和腹腔巨噬细胞，并检测吞噬和杀伤作用。通过腹腔内注射眼镜蛇蛇毒因子（CVF）使 C57BL/6 小鼠产生补体缺陷，并用补体 3（C3）基因敲除小鼠建立 C3 基因敲除小鼠，诱导这些小鼠发生屎肠球菌腹膜炎。在感染后 48 小时内的几个时间点，将感染的进程与生理盐水对照和野生型小鼠进行比较。
补体的调理作用增强了中性粒细胞和巨噬细胞的吞噬作用。CVF 处理组和 C3 基因敲除组在清除所有研究的器官和组织（腹腔液、血液、肺和肝）中的屎肠球菌方面受到严重阻碍。去补体组的腹腔细胞因子和趋化因子水平较高，而系统或腹腔细胞动力学无差异。
补体缺乏严重阻碍了屎肠球菌腹膜炎的清除和随后的全身感染。
