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Abstract # 1776 Upper-respiratory viral infection triggers EAE onset in autoimmune prone T-cell receptor transgenic mice

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system. Most MS patients experience periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Interestingly, upper-respiratory viral infections increase the risk for relapse. Here, we utiliz...

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Bibliographic Details
Published in:Brain, behavior, and immunity behavior, and immunity, 2016-10, Vol.57, p.e20-e20
Main Authors: Blackmore, S, Juda, M, Hernandez, J, Johnson, R.W, Steelman, A.J
Format: Article
Language:English
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Summary:Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system. Most MS patients experience periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Interestingly, upper-respiratory viral infections increase the risk for relapse. Here, we utilized an autoimmune-prone T-cell receptor transgenic mouse (2D2) and a mouse-adapted human influenza virus to test the hypothesis that upper-respiratory viral infection can cause glial activation, promote immune cell trafficking to the CNS and trigger disease. Specifically, we inoculated C57BL/6 mice with the H1N1 strain of influenza A virus (Puerto Rico/8/34; PR8) then measured: Transcriptomic alterations occurring in the cerebellum and spinal cord, immune cell surveillance of the CNS by flow cytometry and chemokine production from primary glial cultures by ELISA. Infected 2D2 mice were monitored for symptoms of inflammatory demyelination. Infection caused temporal alterations in the transcriptome of both the cerebellum and spinal cord that were consistent with glial activation. Infection of C57BL/6 mice increased CD3+CD4+ T-cell trafficking to the brain at day 8 p.i. Cytokine stimulation of primary glial cultures implicated astrocytes as a major source of chemokine production. Finally, clinical and histological EAE was observed in ∼ 27% of infected 2D2 mice. These data identify a new model with which to study how viral infection progresses disease in MS patients and suggests that peripheral infection induced glial activation precedes relapse.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2016.07.069