Leendertse Masja, Willems Rob J L, Giebelen Ida A J, Roelofs Joris J T H, van Rooijen Nico, Bonten Marc J M, van der Poll Tom
Center for Infection and Immunity Amsterdam, Center for Experimental and Molecular Medicine.
Innate Immun. 2009 Feb;15(1):3-12. doi: 10.1177/1753425908100238.
The increasing incidence of infections with multi-drug resistant Enterococcus faecium necessitates studies to increase knowledge on the pathogenesis of these infections. In this study, the contribution of peritoneal macrophages during E. faecium peritonitis was investigated. In an ex vivo setting, peritoneal macrophages harvested from C57BL/6 mice were responsive to, and able to phagocytose and kill, E. faecium. In vivo, peritoneal macrophages were depleted by intraperitoneal injection of clodronate-encapsulated liposomes, prior to inducing E. faecium peritonitis. Depletion of resident peritoneal macrophages caused a clear delay in peritoneal clearance of E. faecium with increased systemic dissemination. Mice depleted of peritoneal macrophages were able to recruit macrophages and neutrophils to the peritoneal cavity after infection, comparable to control mice. Furthermore, increased levels of peritoneal cytokines and chemokines were found in mice depleted of peritoneal macrophages. This study indicates that peritoneal macrophages are important in the early containment of E. faecium peritonitis and for the regulation of the inflammatory response.
耐多药粪肠球菌感染的发病率不断上升,因此有必要开展研究以增进对这些感染发病机制的了解。在本研究中,我们调查了腹膜巨噬细胞在粪肠球菌腹膜炎中的作用。在体外实验中,从C57BL/6小鼠获取的腹膜巨噬细胞对粪肠球菌有反应,并且能够吞噬和杀灭粪肠球菌。在体内实验中,在诱导粪肠球菌腹膜炎之前,通过腹腔注射氯膦酸盐包裹的脂质体来清除腹膜巨噬细胞。驻留腹膜巨噬细胞的清除导致粪肠球菌的腹膜清除明显延迟,全身播散增加。与对照小鼠相比,腹膜巨噬细胞被清除的小鼠在感染后能够将巨噬细胞和中性粒细胞募集到腹腔。此外,在腹膜巨噬细胞被清除的小鼠中发现腹膜细胞因子和趋化因子水平升高。本研究表明,腹膜巨噬细胞在粪肠球菌腹膜炎的早期控制和炎症反应调节中起着重要作用。