Controllable and uncontrollable stress differentially impact pathogenicity and survival in a mouse model of viral encephalitis

• Published in: Journal of neuroimmunology Vol. 319; pp. 130 - 141
• Main Authors: Ciavarra, Richard P., Machida, Mayumi, Lundberg, Patric S., Gauronskas, Phillip, Wellman, Laurie L., Steel, Christina, Aflatooni, Justin O., Sanford, Larry D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2018
• Subjects: Cytokine; Innate immunity; MicroRNA; Neuroinflammation; Stressor controllability; Vesicular stomatitis virus; Vesicular stomatitis virus; Neuroinflammation; Innate immunity; MicroRNA; Stressor controllability; Cytokine
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2018.02.014

Intranasal instillation of vesicular stomatitis virus (VSV) into mice given controllable stress (modeled by escapable foot shock, ES) resulted in enhanced pathogenicity and decreased survival relative to infected mice given uncontrollable stress (modeled by inescapable foot shock, IS) and non-shocked control mice. Survival likely reflected differential cytokine gene expression that may have been regulated by miR146a, a predicted stress-responsive upstream regulator. Controllability also enhanced the accumulation of brain T resident memory cells that persisted long after viral clearance. The unexpected facilitatory effect of ES on antiviral neuroimmune responses and pathogenicity may arise from differential immunoactivating and immunosuppressive effects of uncontrollable and controllable stress. [Display omitted] •Controllable and uncontrollable stress differentially impact viral pathogenicity.•Controllable stress dysregulates cytokine responses following viral neuroinvasion.•Controllable stress decreases survival during viral encephalitis.•Differential stress-related cytokine responses are regulated via miR146a.•Controllable stress increases persistent brain T resident memory cells.