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
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cheeran, M. C.-J.
Right arrow Articles by Lokensgard, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cheeran, M. C.-J.
Right arrow Articles by Lokensgard, J. R.

 Previous Article  |  Next Article 

Journal of Virology, April 2003, p. 4502-4515, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4502-4515.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

CXCL10 Production from Cytomegalovirus-Stimulated Microglia Is Regulated by both Human and Viral Interleukin-10

Maxim C.-J. Cheeran,1,2 Shuxian Hu,1,2 Wen S. Sheng,1 Phillip K. Peterson,1,2 and James R. Lokensgard1,2*

Minneapolis Medical Research Foundation,1 University of Minnesota Medical School, Minneapolis, Minnesota 554042

Received 5 November 2002/ Accepted 31 January 2003

Glial cells orchestrate immunocyte recruitment to focal areas of viral infection within the brain and synchronize immune cell functions through a regulated network of cytokines and chemokines. Since recruitment of T lymphocytes plays a critical role in resolving cytomegalovirus (CMV) infection, we investigated the production of a T-cell chemoattractant, CXCL10 (gamma interferon-inducible protein 10) in response to viral infection of human glial cells. Infection with CMV was found to elicit the production of CXCL10 from primary microglial cells but not from astrocytes. This CXCL10 expression was not dependent on secondary protein synthesis but did require the phosphorylation of p38 mitogen-activated protein (MAP) kinase. In addition, migration of activated lymphocytes toward supernatants from CMV-stimulated microglial cells was partially suppressed by anti-CXCL10 antibodies. Since regulation of central nervous system inflammation is essential to allow viral clearance without immunopathology, microglial cells were then treated with anti-inflammatory cytokines. CMV-induced CXCL10 production from microglial cells was suppressed following treatment with interleukin-10 (IL-10) and IL-4 but not following treatment with transforming growth factor ß. The IL-10-mediated inhibition of CXCL10 production was associated with decreased CMV-induced NF-{kappa}B activation but not decreased p38 MAP kinase phosphorylation. Finally, CMV infection of fully permissive astrocytes resulted in mRNA expression for the viral homologue to human IL-10 (i.e., cmvIL-10 [UL111a]) in its spliced form and conditioned medium from CMV-infected astrocytes inhibited virus-induced CXCL10 production from microglial cells through the IL-10 receptor. These findings present yet another mechanism through which CMV may subvert host immune responses.

* Corresponding author. Mailing address: Minneapolis Medical Research Foundation, 914 S. 8th St., Bldg. D-3, Minneapolis, MN 55404. Phone: (612) 347-6849. Fax: (612) 337-7372. E-mail: jlokensgard{at}mmrf.org.

Journal of Virology, April 2003, p. 4502-4515, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4502-4515.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Slobedman, B., Barry, P. A., Spencer, J. V., Avdic, S., Abendroth, A. (2009). Virus-Encoded Homologs of Cellular Interleukin-10 and Their Control of Host Immune Function. J. Virol. 83: 9618-9629 [Full Text]  
  • Cheeran, M. C.-J., Lokensgard, J. R., Schleiss, M. R. (2009). Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention. Clin. Microbiol. Rev. 22: 99-126 [Abstract] [Full Text]  
  • Harvey, S. A. K., Romanowski, E. G., Yates, K. A., Gordon, Y. J. (2005). Adenovirus-Directed Ocular Innate Immunity: The Role of Conjunctival Defensin-like Chemokines (IP-10, I-TAC) and Phagocytic Human Defensin-{alpha}. IOVS 46: 3657-3665 [Abstract] [Full Text]  
  • Nakamichi, K., Saiki, M., Sawada, M., Takayama-Ito, M., Yamamuro, Y., Morimoto, K., Kurane, I. (2005). Rabies Virus-Induced Activation of Mitogen-Activated Protein Kinase and NF-{kappa}B Signaling Pathways Regulates Expression of CXC and CC Chemokine Ligands in Microglia. J. Virol. 79: 11801-11812 [Abstract] [Full Text]  
  • Rock, R. B., Gekker, G., Hu, S., Sheng, W. S., Cheeran, M., Lokensgard, J. R., Peterson, P. K. (2004). Role of Microglia in Central Nervous System Infections. Clin. Microbiol. Rev. 17: 942-964 [Abstract] [Full Text]  
  • Inngjerdingen, M., Rolstad, B., Ryan, J. C. (2003). Activating and Inhibitory Ly49 Receptors Modulate NK Cell Chemotaxis to CXC Chemokine Ligand (CXCL) 10 and CXCL12. J. Immunol. 171: 2889-2895 [Abstract] [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»