Affiliation:
1. Center for Infection and Immunity Amsterdam (CINIMA)
2. Center for Experimental and Molecular Medicine
3. Department of Medical Microbiology
4. Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
5. Julius Center for Health Studies and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
Abstract
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
57 articles.
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