Upper-respiratory infection triggers experimental autoimmune encephalomyelitis onset in autoimmune prone t-cell receptor transgenic mice

Multiple Sclerosis (MS) is an autoimmune-mediated demyelinating and neurodegenerative disease of the central nervous system. Most MS patients experience a disease course characterized by periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Relapse contributes to disability but the processes that trigger relapses are poorly understood. Upper-respiratory viral infection increases the risk for relapse. Here, we tested the hypothesis that upper respiratory infection is sufficient to cause glial activation, promote immune cell trafficking to the CNS and trigger pathology in an autoimmune-prone T cell receptor transgenic mouse line. To test this hypothesis we infected 2D2 mice and monitored for symptoms of inflammatory demyelination (EAE). Clinical and histological EAE was observed in ~29.2% of infected 2D2 mice which closely resembles the incidence of upper-respiratory infection-induced relapse in MS patients. Chemokine production in brain resident glial cells, primarily astrocytes was induced by TNF and IL-1β stimulation which may assist in the trafficking of immune cells to the CNS. Furthermore, pharmacological inhibitors of JNK, ERK1/2, p38, and NF-κB modulated the levels of chemokines secreted by astrocytes in response to cytokine stimulation. Increased levels of serum IFN-γ were observed in C57BL/6 mice infected with influenza as well as increased CD4+ T-cells in the choroid plexus. Finally, we observed immunosurveillance of the brain by T-cells and CD45highCD11b+ cells in C57BL/6 mice after influenza inoculation. This immunosurveillance could prove detrimental to MS patients.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2017

Author dc:creator

• Blackmore, Stephen Daniel

Contributors dc:contributor

• Steelman, Andrew J.
• Gaskins, H. Rex
• Johnson, Rodney
• Loerch, Steven
• Rodriguez-Zas, Sandra

• Multiple Sclerosis
• Experimental Autoimmune Encephalomyelitis
• Inflammation

Statement dc:rights

• Copyright 2016 Stephen Blackmore

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/95505

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/95505