| 研究実績の概要 |
Macrophage is a professional phagocyte to engulf bacteria into lysosome for digestion. To reach interaction with lysosome, the intracellular bacteria could be transported by phagocytosis and macroautophagy. However, only a part of GAS was surrounded by autophagosome, the majority was by lysosome directly. In macrophage, lysosome membrane is more dynamic and could change shape along with a big cargo directly: lysosome protrusion1. This action also recognized as the lysosome wrapping mechanism (LWM) of microautophagy.
In this year, I found microautophagy was related to GAS killing by lysosome in macrophage, while GAS growth was only slightly affected in macroautophagy defective macrophage, ATG7KO and FIP200KO cells, generated during this year. Using the identified two small GTPase proteins in our group, we had found Rab32 and Rab38 are involved in lysosome vesicle transport. I found Rab32/Rab38 highly recruited to GAS-containing lysosome in macrophage. Lost of Rab32/38 decreased macrophage bacterial clearance. Notice, Rab32 and Rab38 positive ring could not be fixed well by regular formaldehyde. Rab32 or Rab38 have to be observed in life cell conditions, according to our GFP-Rab32 or GFP-Rab38 fusion protein expressing cell observation. As, an innate immune professional cells, macrophage activating response to GAS engulfment was analyed. I found that the inflammatory cytokines, including TNFalpha, IL6 and ROS, were decreased in GAS-infected DKO cells, comparing to WT cells.
|
