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 Olson, J. K.
Right arrow Articles by Miller, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Olson, J. K.
Right arrow Articles by Miller, S. D.

 Previous Article  |  Next Article 

Journal of Virology, October 2001, p. 9780-9789, Vol. 75, No. 20
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.20.9780-9789.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Direct Activation of Innate and Antigen-Presenting Functions of Microglia following Infection with Theiler's Virus

Julie K. Olson, Ann M. Girvin, and Stephen D. Miller*

Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Ilinois 60611

Received 18 May 2001/Accepted 23 July 2001

Microglia are resident central nervous system (CNS) macrophages. Theiler's murine encephalomyelitis virus (TMEV) infection of SJL/J mice causes persistent infection of CNS microglia, leading to the development of a chronic-progressive CD4+ T-cell-mediated autoimmune demyelinating disease. We asked if TMEV infection of microglia activates their innate immune functions and/or activates their ability to serve as antigen-presenting cells for activation of T-cell responses to virus and endogenous myelin epitopes. The results indicate that microglia lines can be persistently infected with TMEV and that infection significantly upregulates the expression of cytokines involved in innate immunity (tumor necrosis factor alpha, interleukin-6 [IL-6], IL-18, and, most importantly, type I interferons) along with upregulation of major histocompatibility complex class II, IL-12, and various costimulatory molecules (B7-1, B7-2, CD40, and ICAM-1). Most significantly, TMEV-infected microglia were able to efficiently process and present both endogenous virus epitopes and exogenous myelin epitopes to inflammatory CD4+ Th1 cells. Thus, TMEV infection of microglia activates these cells to initiate an innate immune response which may lead to the activation of naive and memory virus- and myelin-specific adaptive immune responses within the CNS.

* Corresponding author. Mailing address: Department of Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Phone: (312) 503-7674. Fax: (312) 503-1154. E-mail: s-d-miller{at}nwu.edu.

Journal of Virology, October 2001, p. 9780-9789, Vol. 75, No. 20
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.20.9780-9789.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Bowen, J. L., Olson, J. K. (2009). Innate Immune CD11b+Gr-1+ Cells, Suppressor Cells, Affect the Immune Response during Theiler's Virus-Induced Demyelinating Disease. J. Immunol. 183: 6971-6980 [Abstract] [Full Text]  
  • Donson, A. M., Birks, D. K., Barton, V. N., Wei, Q., Kleinschmidt-DeMasters, B. K., Handler, M. H., Waziri, A. E., Wang, M., Foreman, N. K. (2009). Immune Gene and Cell Enrichment Is Associated with a Good Prognosis in Ependymoma. J. Immunol. 183: 7428-7440 [Abstract] [Full Text]  
  • Olson, J. K., Miller, S. D. (2009). The Innate Immune Response Affects the Development of the Autoimmune Response in Theiler's Virus-Induced Demyelinating Disease. J. Immunol. 182: 5712-5722 [Abstract] [Full Text]  
  • Jin, Y.-H., Mohindru, M., Kang, M. H., Fuller, A. C., Kang, B., Gallo, D., Kim, B. S. (2007). Differential Virus Replication, Cytokine Production, and Antigen-Presenting Function by Microglia from Susceptible and Resistant Mice Infected with Theiler's Virus. J. Virol. 81: 11690-11702 [Abstract] [Full Text]  
  • Ponomarev, E. D., Shriver, L. P., Dittel, B. N. (2006). CD40 Expression by Microglial Cells Is Required for Their Completion of a Two-Step Activation Process during Central Nervous System Autoimmune Inflammation. J. Immunol. 176: 1402-1410 [Abstract] [Full Text]  
  • Croxford, J. L., Olson, J. K., Anger, H. A., Miller, S. D. (2005). Initiation and Exacerbation of Autoimmune Demyelination of the Central Nervous System via Virus-Induced Molecular Mimicry: Implications for the Pathogenesis of Multiple Sclerosis. J. Virol. 79: 8581-8590 [Abstract] [Full Text]  
  • Bradl, M., Bauer, J., Flugel, A., Wekerle, H., Lassmann, H. (2005). Complementary Contribution of CD4 and CD8 T Lymphocytes to T-Cell Infiltration of the Intact and the Degenerative Spinal Cord. Am. J. Pathol. 166: 1441-1450 [Abstract] [Full Text]  
  • Rempel, J. D., Quina, L. A., Blakely-Gonzales, P. K., Buchmeier, M. J., Gruol, D. L. (2005). Viral Induction of Central Nervous System Innate Immune Responses. J. Virol. 79: 4369-4381 [Abstract] [Full Text]  
  • Mendez-Fernandez, Y. V., Hansen, M. J., Rodriguez, M., Pease, L. R. (2005). Anatomical and Cellular Requirements for the Activation and Migration of Virus-Specific CD8+ T Cells to the Brain during Theiler's Virus Infection. J. Virol. 79: 3063-3070 [Abstract] [Full Text]  
  • Croxford, J. L., Anger, H. A., Miller, S. D. (2005). Viral Delivery of an Epitope from Haemophilus influenzae Induces Central Nervous System Autoimmune Disease by Molecular Mimicry. J. Immunol. 174: 907-917 [Abstract] [Full Text]  
  • Olson, J. K., Miller, S. D. (2004). Microglia Initiate Central Nervous System Innate and Adaptive Immune Responses through Multiple TLRs. J. Immunol. 173: 3916-3924 [Abstract] [Full Text]  
  • Nakamichi, K., Inoue, S., Takasaki, T., Morimoto, K., Kurane, I. (2004). Rabies Virus Stimulates Nitric Oxide Production and CXC Chemokine Ligand 10 Expression in Macrophages through Activation of Extracellular Signal-Regulated Kinases 1 and 2. J. Virol. 78: 9376-9388 [Abstract] [Full Text]  
  • Li, Y., Fu, L., Gonzales, D. M., Lavi, E. (2004). Coronavirus Neurovirulence Correlates with the Ability of the Virus To Induce Proinflammatory Cytokine Signals from Astrocytes and Microglia. J. Virol. 78: 3398-3406 [Abstract] [Full Text]  
  • Oleszak, E. L., Chang, J. R., Friedman, H., Katsetos, C. D., Platsoucas, C. D. (2004). Theiler's Virus Infection: a Model for Multiple Sclerosis. Clin. Microbiol. Rev. 17: 174-207 [Abstract] [Full Text]  
  • Palma, J. P., Kwon, D., Clipstone, N. A., Kim, B. S. (2003). Infection with Theiler's Murine Encephalomyelitis Virus Directly Induces Proinflammatory Cytokines in Primary Astrocytes via NF-{kappa}B Activation: Potential Role for the Initiation of Demyelinating Disease. J. Virol. 77: 6322-6331 [Abstract] [Full Text]  
  • John, G. R., Lee, S. C., Brosnan, C. F. (2003). Cytokines: Powerful Regulators of Glial Cell Activation. Neuroscientist 9: 10-22 [Abstract]  
  • Howard, L. M., Neville, K. L., Haynes, L. M., Dal Canto, M. C., Miller, S. D. (2003). CD154 Blockade Results in Transient Reduction in Theiler's Murine Encephalomyelitis Virus-Induced Demyelinating Disease. J. Virol. 77: 2247-2250 [Abstract] [Full Text]  
  • Olson, J. K., Eagar, T. N., Miller, S. D. (2002). Functional Activation of Myelin-Specific T Cells by Virus-Induced Molecular Mimicry. J. Immunol. 169: 2719-2726 [Abstract] [Full Text]  
  • Girvin, A. M., Gordon, K. B., Welsh, C. J., Clipstone, N. A., Miller, S. D. (2002). Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells. Blood 99: 3692-3701 [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»