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bioRxiv · 10.1101/618314

Alterations of the pulmonary immunity are independent of spontaneous pneumonia in an experimental model of ischemic stroke

Farris, B. Y.·Monaghan, K. L.·Amend, C. D.·Zheng, W.·Hu, H.·Coad, J. E.·Ren, X.·Wan, E. C. K.
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Abstract

Stroke-associated pneumonia (SAP) is a major cause of mortality in patients who have suffered from severe ischemic stroke. Although multi-factorial in nature, stroke-induced immunosuppression plays a key role in the development of SAP. Previous studies of focal ischemic stroke induction, using a murine model of transient middle cerebral artery occlusion (tMCAO) have shown that severe brain damage results in massive apoptosis and functional defects of lymphocytes in the spleen, thymus, and peripheral blood. However, how immune alternations in remote tissues lead to a greater susceptibility to lung infections is not well-understood. Importantly, how ischemic stroke alters immune-cell fates, and the expression of cytokines and chemokines in the lungs that directly impact pulmonary immunity, has not been characterized. We report here that ischemic stroke increases the percentage of alveolar macrophages, neutrophils, and CD11b+ dendritic cells (DCs), but reduces the percentage of CD4+ T cells, CD8+ T cells, B cells, natural killer (NK) cells, and eosinophils in the lungs. The depletion of immune cells in the lungs is not caused by apoptosis, cell infiltration to the brain, or spontaneous pneumonia following ischemic stroke as previously described, but correlates with a significant reduction in the levels of multiple chemokines in the lungs, including: CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, CXCL5, CXCL9, and CXCL10. These findings suggest that ischemic stroke negatively impacts pulmonary immunity to become more susceptible for SAP development. Further investigation into the mechanisms that control pulmonary immune alternations following ischemic stroke may identify novel diagnostic or therapeutic targets for SAP.

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Farris, B. Y., Monaghan, K. L., Amend, C. D., Zheng, W., Hu, H., Coad, J. E., Ren, X., Wan, E. C. K.. 2019-04-25. Alterations of the pulmonary immunity are independent of spontaneous pneumonia in an experimental model of ischemic stroke. https://doi.org/10.1101/618314

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