Molecular mechanism of sporozoite infection inducing autophagy of hepatocytes and promoting their development

Autophagy is not only one of the recently discovered intracellular innate immune responses to restrict the development of a variety of intracellular microorganisms, but also the primary target for microorganisms to evade or suppress the host innate immune responses. Preliminary data showed that infection of sporozoites could induce autophagy of exo-erythrocytic forms by hepatocytes. The induction of autophagy couldn’t inhibit, but significantly promote the development of exo-erythrocytic stage in vitro. However, the underlined mechanism of sporozoite-induced hepatocyte autophagy and its promotive role on liver-stage development is still unknown. This project firstly would investigate whether the sporozoite-induced hepatocyte autophagy is dependent on the activation of mTOR/Beclin-1/ATG5. Then, it’ll observe whether the parasite could still normally replicate in the autolysosome. Finally, it would also investigate whether the hepatocyte autophagy could reduce the production of IFN-α/β in the infected hepatocytes through removing the malaria parasite RNA, and/or inhibite the apoptosis of the infected hepatocytes, in order to support the growth of liver-stage. This study could not only shed new light on the escape strategy of exo-erythrocytic stage, but also provide novel clues to design prophylactic stragies against the liver-stage.

Basic Science

Jan 2015 — Dec 2018

$109,831

China