title: Neutrophils are essential for rapid clearance of Enterococcus faecium in mice.
abstract: A progressive increase in infections with multiresistant Enterococcus faecium has been reported, especially in cancer patients and neutropenic patients. Despite its increasing importance as a nosocomial pathogen, knowledge of the pathogenesis of E. faecium infections is highly limited. In this study, we investigated the role of neutrophils during peritonitis with subsequent bacteremia caused by E. faecium. Therefore, we depleted neutrophils by intraperitoneal injections of monoclonal antibody RB6-8C5. Mice were followed for 5 days, and the enterococcal outgrowth and inflammatory response were compared between neutropenic mice and immunoglobulin G-injected control mice. Neutropenic mice demonstrated a severe delay in enterococcal clearance from all cultured organs (peritoneal fluid, blood, and lung and liver tissue). In particular, neutropenic mice remained bacteremic for up to 3 days, whereas all nonneutropenic mice had cleared the bacteria from circulation by 2 days. Furthermore, neutropenic mice displayed elevated peritoneal cytokine and chemokine levels 1 day after the infection and attracted fewer macrophages into the peritoneal cavity. In the circulation, a prolonged elevation of tumor necrosis factor alpha, interleukin-6, and the acute-phase proteins serum amyloid A and complement 3 were measured in neutropenic mice. In conclusion, attraction of neutrophils to the primary site of E. faecium infection is important for a rapid clearance of this bacterium, thereby attenuating a systemic inflammatory response.
authors.affiliation: Center for Infection and Immunity Amsterdam, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. m.leendertse@amc.uva.nl
authors.forename: Masja
authors.initials: M
authors.lastname: Leendertse
authors.forename: Rob J L
authors.initials: RJ
authors.lastname: Willems
authors.forename: Ida A J
authors.initials: IA
authors.lastname: Giebelen
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry / Q000382:microbiology; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology; D001769:Blood / Q000382:microbiology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000032:analysis / Q000097:blood; D016984:Enterococcus faecium / Q000276:immunology*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000276:immunology; D006801:Humans; D007958:Leukocyte Count; D047589:Leukocyte Reduction Procedures; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D009504:Neutrophils / Q000276:immunology*; D010538:Peritonitis / Q000276:immunology / Q000382:microbiology
chemical_list: D016207:Cytokines