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
Google Scholar
Right arrow Articles by Thapa, M.
Right arrow Articles by Carr, D. J. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thapa, M.
Right arrow Articles by Carr, D. J. J.

 Previous Article  |  Next Article 

Journal of Virology, September 2009, p. 9486-9501, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00854-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

CXCR3 Deficiency Increases Susceptibility to Genital Herpes Simplex Virus Type 2 Infection: Uncoupling of CD8+ T-Cell Effector Function but Not Migration{triangledown}

Manoj Thapa1,{dagger} and Daniel J. J. Carr1,2*

Departments of Microbiology and Immunology,1 Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731042

Received 27 April 2009/ Accepted 30 June 2009

CXCR3 is a G-protein-coupled receptor preferentially expressed by activated T cells, NK cells, and dendritic cells. Signaling through gamma interferon-regulated chemokines CXCL9, CXCL10, CXCL11, and CXCR3 plays a critical role in the immune response of many viral pathogens. However, the relevance of CXCR3 for optimal T-cell activation and the induction of regulatory transcription factors (i.e., T-bet and eomesodermin) relative to host immune defense against genital herpes simplex virus type 2 (HSV-2) infection have been poorly defined. In this study, we evaluated the requirement of CXCR3 expression during genital HSV-2 infection using mice deficient in CXCR3 (CXCR3–/–) along with wild-type (WT) controls, assessing the resistance of mice to viral infection and focusing on the cytokine/chemokine response, phenotypic analysis of recruited leukocytes, and functional analysis of CD8+ T cells. CXCR3–/– mice showed a heightened sensitivity to infection compared to WT animals in terms of the viral burden in infected tissues as well as elevated mortality. The poor response of CXCR3–/– mice to viral infection was associated with reduced cytotoxic T-lymphocyte activity through the impairment of T-bet, perforin, and granzyme B expression by CD8+ T cells. Corresponding with the defective cytolytic activity, a reduction in recruitment of plasmacytoid dendritic cells and CD80 expression in CD11c+ dendritic cells in the draining lymph nodes of CXCR3–/– mice were detected. Collectively, the results provide a new perspective to CXCR3 signaling for the appropriate activation of CD8+ T cells required for host defense against genital HSV-2 infection.

* Corresponding author. Mailing address: Department of Ophthalmology, DMEI no. 415, the University of Oklahoma Health Sciences Center, 608 Stanton L Young Blvd., Oklahoma City, OK 73104. Phone: (405) 271-8784. Fax: (405) 271-8781. E-mail: dan-carr{at}ouhsc.edu

{triangledown} Published ahead of print on 8 July 2009.

{dagger} Present address: Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030.

Journal of Virology, September 2009, p. 9486-9501, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00854-09
Copyright © 2009, 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»