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Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):E6107-E6116. doi: 10.1073/pnas.1620415114. Epub 2017 Jul 10.

Influenza infection triggers disease in a genetic model of experimental autoimmune encephalomyelitis.

Author information

1
Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801.
2
Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL 61801.
3
Department of Pathology, University of Illinois Urbana-Champaign, Urbana, IL 61801.
4
Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801.
5
Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801; asteelma@illinois.edu.

Abstract

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 used 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 2D2 mice with influenza A virus (Puerto Rico/8/34; PR8) and then monitored them for symptoms of inflammatory demyelination. Clinical and histological experimental autoimmune encephalomyelitis was observed in ∼29% of infected 2D2 mice. To further understand how peripheral infection could contribute to disease onset, we inoculated wild-type C57BL/6 mice and measured transcriptomic alterations occurring in the cerebellum and spinal cord and monitored immune cell surveillance of the CNS by flow cytometry. Infection caused temporal alterations in the transcriptome of both the cerebellum and spinal cord that was consistent with glial activation and increased T-cell, monocyte, and neutrophil trafficking to the brain at day 8 post infection. Finally, Cxcl5 expression was up-regulated in the brains of influenza-infected mice and was elevated in cerebrospinal fluid of MS patients during relapse compared with specimens acquired during remission. Collectively, these data identify a mechanism by which peripheral infection may exacerbate MS as well as other neurological diseases.

KEYWORDS:

experimental autoimmune encephalomyelitis; immune cell surveillance; multiple sclerosis; neuroinflammation; upper-respiratory viral infection

PMID:
28696309
DOI:
10.1073/pnas.1620415114

Conflict of interest statement

The authors declare no conflict of interest.

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