This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Traeger, T.
Right arrow Articles by Maier, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Traeger, T.
Right arrow Articles by Maier, S.

 Previous Article  |  Next Article 

Infection and Immunity, November 2008, p. 5285-5293, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00310-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Detrimental Role of CC Chemokine Receptor 4 in Murine Polymicrobial Sepsis{triangledown}

Tobias Traeger,1,{dagger}* Wolfram Kessler,1,{dagger} Volker Assfalg,2 Katharina Cziupka,1 Pia Koerner,1 Constanze Dassow,1 Katrin Breitbach,3 Marlene Mikulcak,1 Ivo Steinmetz,3 Klaus Pfeffer,4 Claus-Dieter Heidecke,1 and Stefan Maier1

Department of Surgery, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany,1 Department of Surgery, Technische Universität München, Munich, Germany,2 Friedrich-Loeffler-Institute of Medical Microbiology, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany,3 Institute of Medical Microbiology, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany4

Received 9 March 2008/ Returned for modification 13 June 2008/ Accepted 25 August 2008

CC chemokine receptor 4 (CCR4) and its two ligands, CCL17 and CCL22, are critically involved in different immune processes. In models of lipopolysaccharide-induced shock, CCR4-deficient (CCR4–/–) mice showed improved survival rates associated with attenuated proinflammatory cytokine release. Using CCR4–/– mice with a C57BL/6 background, this study describes for the first time the role of CCR4 in a murine model of polymicrobial abdominal sepsis, the colon ascendens stent peritonitis (CASP). CASP-induced sepsis led to a massive downregulation of CCR4 in lymphoid and nonlymphoid tissues, whereas the expression of CCL17 and CCL22 was independent of the presence of CCR4. After CASP, CCR4–/– animals showed a strongly enhanced bacterial clearance in several organs but not in the peritoneal lavage fluid and the blood. In addition, significantly reduced levels of proinflammatory cytokines/chemokines were measured in organ supernatants as well as in the sera of CCR4–/– mice. CCR4 deficiency consequently resulted in an attenuated severity of systemic sepsis and a strongly improved survival rate after CASP or CASP with intervention. Thus, our data provide clear evidence that CCR4 plays a strictly detrimental role in the course of polymicrobial sepsis.

* Corresponding author. Mailing address: Klinik für Chirurgie, Abteilung für Allgemeine Chirurgie, Viszeral- Thorax- und Gefässchirurgie, Friedrich-Loeffler-Str. 23b, 17475 Greifswald, Germany. Phone: 49-3834-86-6001. Fax: 49-3834-86-6016. E-mail: traeger{at}uni-greifswald.de

{triangledown} Published ahead of print on 2 September 2008.

Editor: F. C. Fang

{dagger} T.T. and W.K. contributed equally to this work.

Infection and Immunity, November 2008, p. 5285-5293, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00310-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»