Mechanisms of Cytosolic Clearance of Rickettsiae

立克次体的胞质清除机制

基本信息

批准号：
8638611
负责人：
Rong Megan Fang
金额：
$ 23.22万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8638611
关键词：
Actins Affect Applications Grants Autophagocytosis Autophagosome Bacteria Biological C57BL/6 Mouse Case Study Caspase-1 Cells Communicable Diseases Confocal Microscopy Cytoplasm Dependence Disease Dose Event Faculty Figs - dietary Future Human Immune Immunity In Vitro Infection Inflammatory Response Interleukin-1 Invaded Knockout Mice Lead Life Liver Lysosomes Mediating Microbe Modeling Mus Natural Immunity Persons Phagocytosis Phagosomes Preventive Intervention Process Proteins Public Health Regulation Research Research Personnel Rickettsia Rickettsia Infections Role Staging System Testing Therapeutic Intervention Tissues Vacuole adaptive immunity base experience granulocyte in vivo inhibitor/antagonist innovation insight interleukin-1beta-converting enzyme inhibitor killings macrophage mortality mouse model novel novel strategies pathogen public health relevance response weapons

项目摘要

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.

立克次体是细胞内细菌，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、快速逃离吞噬体液泡并在宿主细胞中复制的能力。自噬以自噬体中的细胞质成分为目标，并在自噬体中降解它们。自噬现在被认为是细胞内监测的基石。该系统的目标是确定立克次体与自噬和自噬的相互作用。我们发现立克次体在宿主控制致命性立克次体疾病方面的贡献。感染的早期阶段，介导胞质立克次体的降解，从而产生有效的宿主致命性立克次体疾病的保护性免疫在第一个目标中，我们将确定自噬是否是。由立克次体诱导，以及自噬是否有助于宿主控制致命的立克次体疾病在第二个目标中，我们将确定自噬如何调节 IL-1¿致命期间的响应该项目的成功完成将凸显自噬在宿主控制中的作用。拟议的项目将为靶向自噬提供重要信息。细胞内微生物引起的致命传染病的预防和治疗干预。