Stroke-associated pneumonia impairs neurological recovery through upregulation of interferon signaling in mice 3035

Abstract Description Pneumonia is a major clinical complication of stroke that leads to poor outcomes by increasing mortality and long-term deficits. Peripheral immunodepression, induced by stroke, is a leading cause for higher susceptibility to pneumonia. Unfortunately, the mechanisms of how pneumonia effects brain recovery from stroke is understudied. To study this, stroke was modeled using transient middle cerebral artery occlusion (tMCAO) for 1hr, followed by reperfusion, or mice received sham surgery. On d3 mice either received intratracheal inoculation of Klebsiella pneumoniae or vehicle. Physiological responses, including weight and temperature, behavioral responses, and immune infiltration was measured on d7 and d30 to determine the effect of Klebsiella on brain recovery. We found that tMCAO induces immunodepression in the body with lower white blood cells, specifically neutrophils, in stroked mice + pneumonia, compared to sham mice + pneumonia. Of mice who received a stroke, infected mice had worse neurological deficits and a significantly higher CD45+ infiltration into the stroked hemisphere. CD8+ T cells showed a significant reduction in IFNy and IL-6 production, and Ly6G+ neutrophils showed a significant decrease in TNF and IFNy production after stroke + infection by intracellular cytokine FACS. This data, alongside preliminary scRNAseq data, points to changes in interferon responses in immune cells after stroke + infection that lead to poor recovery and long-term deficits. Topic Categories Neuroimmunology (NEUR)