Mechanisms of Cytosolic Clearance of Rickettsiae

立克次体的胞质清除机制

基本信息

批准号：
8829741
负责人：
Rong Megan Fang
金额：
$ 19.38万
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 2017-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8829741
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 Health 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 response weapons

项目摘要

DESCRIPTION (provided by applicant): Rickettsiae are intracellular bacteria that potentially cause life-threatening diseases all over th 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 determie 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.

描述（由申请人提供）：人力体是细胞内细菌，可能会在世界范围内引起威胁生命的疾病。立克西亚具有侵入宿主细胞，迅速逃脱吞噬液泡并在细胞质中复制的能力。自噬靶向细胞质构成自噬体，并在自溶性/溶酶体中降解它们。自噬现在被认为是细胞内监视系统的基石。拟议项目的目的是确定立克西亚与自噬的相互作用及其贡献托管致命的立克疾病的控制。我们假设立克斯氏症在感染的早期诱导自噬，从而介导胞质立克的降解，从而导致有效的宿主保护性疾病的宿主保护性免疫。在第一个目的中，我们将确定是否是由立克西亚（Rickettsiae）诱导的自噬，以及自噬是否使用小鼠模型有助于宿主对致命身份疾病的控制。在第二个目标中，我们将确定自噬如何调节致命身分疾病期间的IL-1反应。该项目的成功完成将突出自噬在细胞内病原体的宿主控制中的作用。拟议的项目将提供有关针对自噬的重要信息，以进行由细胞内微生物引起的致命感染疾病的预防和治疗干预措施。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The role of autophagy in microbial infection and immunity.

DOI：
10.2147/itt.s76720
发表时间：
2015
期刊：
ImmunoTargets and therapy
影响因子：
7.2
作者：
Desai M;Fang R;Sun J
通讯作者：
Sun J

Rickettsia australis Activates Inflammasome in Human and Murine Macrophages.

DOI：
10.1371/journal.pone.0157231
发表时间：
2016
期刊：
PloS one
影响因子：
3.7
作者：
Smalley C;Bechelli J;Rockx-Brouwer D;Saito T;Azar SR;Ismail N;Walker DH;Fang R
通讯作者：
Fang R

The role of Rhipicephalus sanguineus sensu lato saliva in the dissemination of Rickettsia conorii in C3H/HeJ mice.

血扇头象唾液在 C3H/HeJ 小鼠康氏立克次体传播中的作用。