Inhibition of CD147 Attenuates Stroke-Associated Pneumonia Through Modulating Lung Immune Response in Mice

Background and Purpose: Acute ischemic stroke triggers a profound systemic and local immunodysfunction that increased the susceptibility to infections, especially stroke-associated pneumonia (SAP). Our previous study has shown that inhibition of CD147 ameliorates acute ischemic stroke, however, the role of CD147 in post-stroke lung infection has not been investigated. Methods: C57BL/6 mice were subjected to transient (60min) middle cerebral artery occlusion, and treated with anti-CD147 antibody (alpha CD147). Lung histological changes, vascular permeability, and pulmonary edema were determined. Bacterial burden in the lung tissue and Broncho alveolar lavage fluid (BALF) were measured. Lung leukocyte infiltration, circulating platelet-leukocyte aggregates, cell type-specific IL-17A, and IFN-gamma expression in the lung were detected by flow cytometry. Results: CD147 expression was markedly upregulated in the lung after stroke. alpha CD147 treatment significantly decreased the stroke-associated lung histological damages, bacterial load, vascular permeability and pulmonary edema. The protective effects by a CD147 treatment were associated with deceased lung inflammatory cell infiltration by reducing IL-17A expression in lung gamma delta T cells and attenuated bacterial load by enhancing IFN-gamma expression in the lung NK1.1(+) cells and CD4(+) T cells. In addition, CD147 expression was also increased in the circulating platelets and leukocytes. Enhanced platelet-leukocyte aggregates following stroke was inhibited by alpha CD147 treatment. Conclusions: Inhibition of CD147 ameliorates aberrant lung inflammatory and immune response and reduces bacterial infection after stroke. CD147 might represent a novel and promising therapeutic target for post-stroke lung infection.