Abstract TMP29: Mesenchymal Stromal Cell Administration Attenuates Post-Stroke Susceptibility to Spontaneous Infection Through Prevention of Caspase-1-Dependent Splenic Marginal Zone B Cell Death

Abstract

Spontaneous infection is one of most common complications of acute ischemic stroke (AIS) and leads to increased mortality and morbidity in stroke patients. However, current interventions fail to improve clinical outcomes in these patients. Since stroke-induced immunodeficiency is thought to contribute to the risk of infections, we suppose mesenchymal stromal cells (MSCs) therapy, based on its potent immunomodulatory capacities, could be a potential solution to this problem. Here, we show MSCs administration successfully ameliorates post-stroke infections and reduces the mortality in mouse middle cerebral artery occlusion (MCAO) model of AIS. Additionally, the intravenously infused MSCs preferentially migrate to the spleen and mainly distribute around the marginal zone (MZ). These grafted MSCs rescue stroke-induced splenic atrophy, especially the marginal zone B (MZB) cells loss, a subset of innate-like lymphocytes localized in MZ. Using the CD19-deficient mice model lacking MZB cells, we found that MSCs transplantation could not reduce post-stroke infections or mortality in CD19 -/- mice, reconfirming MZB cells are indispensable for the immunoprotective effects of MSCs. In terms of mechanism, we demonstrate that MSCs attenuate caspase-1-dependent MZB cells death partially through direct mitochondrial transfer and subsequent inhibition of NLRP3 activation. Taken together, this study suggests MSCs administration alleviates post-stroke immunodepression and spontaneous infections via MZB cells protection.