Rapamycin Regulates Lipopolysaccharide-Induced Microglial Phagocytosis In Vitro

Microglia phagocytosis plays an important role in the pathogenesis of neurodegeneration. Defects or dysfunction of microglia phagocytosis were observed in neurodegenerative diseases, with different targets and associated receptors influencing the microglia response. Moreover, non-canonical LC3-associated (microtubule-associated protein 1 light chain 3) phagocytosis was extensively studied recently as a novel form of phagocytosis on macrophages, but little on microglia. Here, we investigated changes in phagocytic function of microglia activated by lipopolysaccharide (LPS) as well as rapamycin-regulated phagocytosis. Phagocytosis in mouse BV2 cells and primary microglia was analyzed by flow cytometry and immunofluorescence. Phagocytosis-related mechanisms in BV2 cells were analyzed using Western blotting and real-time polymerase chain reaction. Rapamycin was shown to reduce LPS-induced phagocytosis of microglia and at the same time stimulate LC3-dependent phagocytosis by regulating Atg3, Atg4 and Atg7 expression. In addition, in BV2 cells, the PI3K/AKT/mTOR pathway may be involved in phagocytosis. These results suggest that phagocytosis of microglia is a complex process, and the increase in phagocytosis should not be considered as a maturation of phagocytic function. The data will provide new insights into the mechanisms of phagocytosis and neuroimmunity.