Autophagy inhibition promotes phagocytosis of macrophage and protects mice from methicillin-resistant staphylococcus aureus pneumonia.

The present study is to investigate the effect of autophagy in macrophages and the protection of mouse models against MRSA invasion, which provide new potential therapeutic direction for lung infection. The effect of ST239 in macrophages were analyzed by Western blot. The immunofluorescence was used to observe the influence of autophagy inhibitor 3-MA in macrophages. Then we established MRSA mice model and the models were divided into different groups of drugs. The effect of autophagy in macrophage with MRSA and the changes of lung pathological in the mouse model was analyzed by flow cytometry and immunohistochemistry. The ability of phagocytic decreases when ST239 infected the macrophages. And the autophagy-related genes Beclin-1, LC3-I, and LC3-II protein expression significantly increased. GFP-LC3 immunostaining showed that GFP-LC3 was significantly over-expressed in ST239-infected macrophages. Then we found the autophagy inhibitors 3-MA could make the expression of autophagy-related genes Beclin-1, LC3-I, and LC3-II decreased, the number of ST239 decreased, and the ability of macrophages phagocytosed MRSA increasing. In the mouse model we performed the same assay, the results showed that the percentage of macrophages in the mouse model treated with 3-MA was increased compared to the ST239 mouse model and that the number of bacteria in right lung significantly reduced. Lung cells treated with3-MA significantly improved the lesion of ST239 lung cell disease. Inhibition of autophagy can increase the ability of macrophages phagocytosed MRSA, and it is a suitable target for preventing or treating MRSA infection.