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 HighWire
Google Scholar
Right arrow Articles by Nguyen, Q.-T.
Right arrow Articles by Kim, B.-S.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nguyen, Q.-T.
Right arrow Articles by Kim, B.-S.

 Previous Article  |  Next Article 

Infection and Immunity, September 2009, p. 3932-3938, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00407-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Blockade of CD137 Signaling Counteracts Polymicrobial Sepsis Induced by Cecal Ligation and Puncture{triangledown}

Quang-Tam Nguyen,1,4 Seong-A Ju,2 Sang-Min Park,1 Sang-Chul Lee,2 Hideo Yagita,3 In Hee Lee,5 and Byung-Sam Kim1*

Life Sciences Research Center and Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea,1 Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Ulsan 680-749, Republic of Korea,2 Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan,3 Department of Biochemistry, Faculty of Biology, University of Natural Sciences, Hochiminh City, Vietnam,4 Department of Bio-Technology, Hoseo University, 29-1 Sechuli, Baebang-Myun, Asan City, Chungnam-Do 336-795, Republic of Korea5

Received 11 April 2009/ Returned for modification 14 May 2009/ Accepted 16 June 2009

Sepsis, a leading cause of death worldwide, involves proinflammatory responses and inefficient bacterial clearance. Previously, we have shown that CD137 (4-1BB), a member of the tumor necrosis factor receptor superfamily, plays critical roles in eradicating infective Listeria monocytogenes, a gram-positive bacterium, and that stimulation of CD137 protects mice from sepsis-induced death. In this study, we unexpectedly found that CD137 activation aggravated polymicrobial sepsis due to mixed gram-positive and gram-negative bacterial infection induced by cecal ligation and puncture (CLP). CD137-deficient (CD137–/–) mice showed significantly lower mortality than CD137-sufficient (CD137+/+) mice in the CLP model. Administration of an agonistic anti-CD137 monoclonal antibody (MAb) to CD137+/+ mice decreased their survival in this infection model, while administration of a blocking anti-CD137 ligand MAb (TKS-1) to such mice increased their survival. CD137–/– mice and TKS-1-treated CD137+/+ mice had lower levels of chemokines/proinflammatory cytokines (monocyte chemoattractant protein 1, interleukin-6 [IL-6], tumor necrosis factor alpha, IL-12) and an anti-inflammatory cytokine (IL-10), exhibited improved bacterial clearance in the peritoneum, liver, and blood, and had greater numbers of infiltrated peritoneal neutrophils and macrophages in the CLP model than control mice. Our data suggest that CD137 activation aggravates polymicrobial sepsis induced by CLP.

* Corresponding author. Mailing address: Life Sciences Research Center and Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea. Phone: 82-52-259-1541. Fax: 82-52-259-2740. E-mail: bskim{at}mail.ulsan.ac.kr

{triangledown} Published ahead of print on 29 June 2009.

Editor: F. C. Fang

Infection and Immunity, September 2009, p. 3932-3938, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00407-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vickers, M. (2009). The doctor's dilemma: stimulating T cells. Blood 114: 3361-3362 [Full Text]  


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