http://jvi.asm.org/cgi/content/abstract/79/7/4369
Journal of Virology, April 2005, p. 4369-4381, Vol. 79, No. 7
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.7.4369-4381.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Viral Induction of Central Nervous System Innate Immune Responses
J. D. Rempel, L. A. Quina, P. K. Blakely-Gonzales, M. J. Buchmeier,, and D. L. Gruol*
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California
Received 28 July 2004/ Accepted 9 November 2004
The ability of the central nervous system (CNS) to generate innate immune responses was investigated in an in vitro model of CNS infection. Cultures containing CNS cells were infected with mouse hepatitis virus-JHM, which causes fatal encephalitis in mice. Immunostaining indicated that viral infection had a limited effect on culture characteristics, overall cell survival, or cell morphology at the early postinfection times studied.
Results from Affymetrix gene array analysis, assessed on RNA isolated from virally and sham-infected cultures, were compared with parallel protein assays for cytokine, chemokine, and cell surface markers. Of the 126 transcripts found to be differentially expressed between viral and sham infections, the majority were related to immunological responses.
Virally induced increases in interleukin-6 and tumor necrosis factor alpha mRNA and protein expression correlated with the genomic induction of acute-phase proteins. Genomic and protein analysis indicated that viral infection resulted in prominent expression of neutrophil and macrophage chemotactic proteins. In addition, mRNA expression of nonclassical class I molecules H2-T10, -T17, -M2, and -Q10, were enhanced three- to fivefold in virus-infected cells compared to sham-infected cells.
Thus, upon infection, resident brain cells induced a breadth of innate immune responses that could be vital in directing the outcome of the infection and, in vivo, would provide signals which would summon the peripheral immune system to respond to the infection. Further understanding of how these innate responses participate in immune protection or immunopathology in the CNS will be critical in efforts to intervene in severe encephalitis.
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* Corresponding author. Mailing address: Department of Neuropharmacology, CVN 11, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-7060. Fax: (858) 784-7393. E-mail: gruol@scripps.edu.
Present address: Section of Hepatology, Internal Medicine/Immunology, University of Manitoba, Winnipeg, Manitoba R3E 3P4, Canada.
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Journal of Virology, April 2005, p. 4369-4381, Vol. 79, No. 7
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.7.4369-4381.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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