The Impact of Social Stress on Central Nervous System Inflammation and T Cell Response to Theiler?s Virus Infection
Vichaya, Elisabeth Good
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A growing body of evidence suggests that social stress contributes to the pathogenesis of neurodegenerative diseases, such as multiple sclerosis (MS). For example, prior research has shown that social disruption (SDR) stress behaviorally and immunologically exacerbates Theiler?s murine encephalomyelitis virus (TMEV) infection. TMEV infection results in acute infection of the central nervous system (CNS) followed by a chronic demyelinating autoimmune disease, similar to that seen in MS. Research suggests that social stress exerts these effects by altering the immune response to infection. More specifically, it is hypothesized that SDR sensitizes the acute inflammatory response to infection and suppresses T cell effector function in the acute phase of disease. It was demonstrated that SDR is sufficient to alter inflammation. Exposure to a single session of SDR increases IL-??1? mRNA expression; however, IL-??6 mRNA expression, but not IL-??1?, is up regulated in response to chronic SDR. Furthermore, chronic SDR prior to infection resulted in increased infection related central IL-??6 and IL-??1? mRNA expression, and central administration of IL-??6 neutralizing antibody during SDR reverses this increase in neuroinflammation. This suggests that SDR sensitizes infection related CNS inflammation through an up-??regulation of IL-??6. Chronic SDR prior to infection also resulted in enhanced CNS viral titers and suppression of virus-??induced CD4 and CD8 T cell IFN-??? release within the CNS. As a whole, this research indicates that SDR exacerbates the disease course of TMEV infection by altering the central innate and adaptive immune response to infection. This research enhances our understanding of the mechanisms by which social stress exacerbates neurodegenerative disease pathogenesis.