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Glia Specific Innate Responses and Their Influence on Murine Coronavirus Inducedencephalomyelitis

Kapil, Parul
http://rave.ohiolink.edu/etdc/view?acc_num=csu1333590615

Abstract Details

2011, Doctor of Philosophy in Regulatory Biology, Cleveland State University, College of Sciences and Health Professions.
Control of viral infections of the central nervous system (CNS) is challenging, as the host has to balance anti-viral activity and immune mediated damage to non- renewable cells. The present study focuses on the role of glia and macrophages in regulating initial viral control and subsequent T cell activity in a murine model of neurotropic coronavirus induced encephalomyelitis. As induction of IFNα/β, pro- and anti-inflammatory factors depend on activation of pattern recognition receptors (PRR), macrophages, microglia and oligodendroglia were isolated from the CNS of infected mice to characterize their gene expression patterns. Oligodendroglia did not induce Ifnα/β expression following intracranial inoculation of both virus or the PRR agonist poly I:C, consistent with limited expression of PRRs and factors critical in the IFNα/β pathway. By contrast, induction of Ifnα/β by infected microglia and macrophages coincided with a broad and high basal expression pattern of IFNα/β signaling components and a protective antiviral state. Furthermore, an anti-inflammatory property of IFNα/β was suggested by abrogation of early Il1ra expression in both microglia and macrophage in the absence of IFNα/β signaling. Microglia and macrophages also induced a mixture of pro-inflammatory (Il12) and anti–inflammatory (Il1ra, Ym1/2) genes, which shape the adaptive immune response. IL12 and Ym1/2 stimulate T cells towards IFNγ and IL13 producing cells, respectively. The absence of IL12 decreased IFNγ and increased IL10 production, resulting in amelioration in clinical disease without altering virus control. Under the influence of distinct T cell mediated stimuli both microglia and macrophage retained a mixed pro- and anti-inflammatory phenotype defined by increased expression of iNos and Arg1, respectively. Sustained expression of Arg1 and increased phagocytic activity indicated an overall bias towards an anti-inflammatory phenotype with time. Finally, analysis of the role of PKR, an IFNα/β induced anti-viral gene, demonstrated only a modest direct anti-viral role. Surprisingly however, PKR deficiency reduced production of the anti-inflammatory cytokine IL10 by CD4 T cells, coincident with increased diffuse demyelination. These results demonstrate how a tightly linked network between innate and adaptive responses regulates viral control as well as tissue damage and disease in a viral encephalomyelitis model.  
Cornelia Bergmann, PhD (Advisor)
Crystal Weyman, PhD (Committee Member)
Robert Silverman, PhD (Committee Member)
Vincent Tuohy, PhD (Committee Member)
William Baldwin, MD, PhD (Other)
Bruce Lamb, PhD (Other)
Immunology; Neurosciences
coronavirus; encephalomyelitis; innate immune response; glial cells

Recommended Citations

Citations

  • Kapil, P. (2011). Glia Specific Innate Responses and Their Influence on Murine Coronavirus Inducedencephalomyelitis [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1333590615

    APA Style (7th edition)

  • Kapil, Parul. Glia Specific Innate Responses and Their Influence on Murine Coronavirus Inducedencephalomyelitis. 2011. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1333590615.

    MLA Style (8th edition)

  • Kapil, Parul. "Glia Specific Innate Responses and Their Influence on Murine Coronavirus Inducedencephalomyelitis." Doctoral dissertation, Cleveland State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=csu1333590615

    Chicago Manual of Style (17th edition)

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© 2011, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.