The complement system facilitates clearance of Enterococcus faecium during murine peritonitis.
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.


CONCLUSIONS
Complement deficiency severely hampers the clearance of E. faecium peritonitis and subsequent systemic infection.
Leendertse
Masja
M
Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam. The Netherlands. m.leendertse@amc.uva.nl
Willems
Rob J L
RJ
Flierman
Roelof
R
de Vos
Alex F
AF
Bonten
Marc J M
MJ
van der Poll
Tom
T
D000818:Animals; D018925:Chemokines / Q000276:immunology; D003176:Complement C3 / Q000235:genetics / Q000276:immunology; D051056:Complement Inactivating Agents / Q000494:pharmacology; D003165:Complement System Proteins / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000494:pharmacology; D016984:Enterococcus faecium / Q000276:immunology*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D010538:Peritonitis / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D018709:Statistics, Nonparametric
D018925:Chemokines; D003176:Complement C3; D051056:Complement Inactivating Agents; D016207:Cytokines; D004546:Elapid Venoms; C016310:cobra venom factor; D003165:Complement System Proteins