Mechanisms of Cytosolic Clearance of Rickettsiae

立克次氏体是一种细胞内细菌，可能在世界各地引起危及生命的疾病。 立克次体具有侵入宿主细胞、迅速逃离吞噬体空泡并在宿主细胞内复制的能力。 细胞质自噬靶向自噬体中的细胞质成分，并在细胞内降解它们。 自体溶酶体/溶酶体。自噬被认为是细胞内监视的基石 系统该项目的目的是确定立克次体与自噬的相互作用， 其对宿主控制致命性立克次体疾病的贡献。我们假设立克次体在一定程度上诱导自噬， 感染的早期阶段，介导胞质立克次体的降解，导致有效宿主 致命立克次体病的保护性免疫。在第一个目标中，我们将确定自噬是否是 以及自噬是否有助于宿主控制致命性立克次体病， 小鼠模型在第二个目标中，我们将确定自噬如何调节IL-1应答， 立克次体病该项目的成功完成将突出自噬在宿主控制中的作用 细胞内的病原体。拟议的项目将提供关于靶向自噬的重要信息， 预防和治疗由细胞内微生物引起的致命传染病。

Rickettsiae are intracellular bacteria that potentially cause life-threatening diseases all over the world. Rickettsiae possess the ability to invade host cells, quickly escape phagosomal vacuoles, and replicate in the cytoplasm. Autophagy targets cytoplasmic constituents in the autophagosomes and degrades them in the autolysosomes/lysosomes. Autophagy is now considered as a cornerstone of the intracellular surveillance system. The objective of the proposed project is to determine the interaction of rickettsiae with autophagy and its contribution to host control of fatal rickettsial diseases. We hypothesize that rickettsiae induce autophagy at the early stage of infection, which mediates degradation of cytosolic rickettsiae resulting in efficient host protective immunity of fatal rickettsial diseases. In the first Aim, we will determine whether autophagy is induced by rickettsiae and whether autophagy contributes to host control of fatal rickettsial diseases using a mouse model. In the second aim, we will identify how autophagy regulates the IL-1¿ response during fatal rickettsial diseases. The successful completion of the project will highlight the role of autophagy in host control of intracellular pathogens. The proposed project will provide important information on targeting autophagy for preventive and therapeutic interventions of fatal infectious diseases caused by intracellular microbes.