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Infection and Immunity, January 2009, p. 485-491, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00863-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Neutrophils Are Essential for Rapid Clearance of Enterococcus faecium in Mice{triangledown}

Masja Leendertse,1,2,4* Rob J. L. Willems,4 Ida A. J. Giebelen,1,2 Joris J. T. H. Roelofs,3 Marc J. M. Bonten,4,5 and Tom van der Poll1,2

Center for Infection and Immunity Amsterdam (CINIMA),1 Center for Experimental and Molecular Medicine,2 Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands,3 Department of Medical Microbiology,4 Julius Center for Health Studies and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands5

Received 14 July 2008/ Returned for modification 11 August 2008/ Accepted 29 October 2008

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.

* Corresponding author. Mailing address: Center for Experimental and Molecular Medicine, Room G2-130, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Phone: 31-20-5665910. Fax: 31-20-6977192. E-mail: m.leendertse{at}amc.uva.nl

{triangledown} Published ahead of print on 10 November 2008.

Editor: B. A. McCormick

Infection and Immunity, January 2009, p. 485-491, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00863-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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