Intestinal epithelial cell exfoliation by caspases

Caspases 导致肠上皮细胞脱落

基本信息

批准号：
10395547
负责人：
Edward A Miao
金额：
$ 44.28万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-03 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10395547
关键词：
Adherence Adhesions Animals Apoptosis Apoptotic Back Bacteria Bacterial Infections Bacterial Translocation Body Surface Area CASP1 gene CASP3 gene CASP7 gene Cardiovascular system Caspase Cell Death Cell Line Cell membrane Cells Coculture Techniques Cytosol Data Epithelial Cells Event Exposure to Family Flagellin Focal Adhesions Grant Immune Immune system In Vitro Infection Inflammasome Inflammatory Inflammatory Bowel Diseases Interleukin-1 beta Interleukin-18 Intestines Invaded Link Lymphocyte Lytic Methods Microbe Mind Mus Needles Nutrient Oral Organoids Oxygen Pathway interactions Proteins Rod Role Salmonella typhimurium Signal Pathway Signal Transduction Surveys System Type III Secretion System Pathway Virulence Factors cell type crosslink extracellular fighting gastrointestinal infection gut colonization in vivo intestinal epithelium intraepithelial lambda Spi-1 macrophage member novel oral infection pathogen pathogenic bacteria programs sensor

项目摘要

ABSTRACT Many bacterial pathogens attempt to adhere to or invade intestinal epithelial cells (IECs), often using virulence factors that manipulate cytosolic signaling pathways in the IEC. However, IECs are able to survey their cytosol by using innate immune sensors in the inflammasome family. We have shown that inflammasomes can detect the activity of bacterial secretion systems by detecting aberrant translocation of bacterial flagellin, rod, and needle proteins. Inflammasomes have largely been studied in macrophages, where active caspase-1 was first shown to cleave pro-IL-1β and pro-IL-18 to their mature and released forms. Caspase-1 was recently shown to cleave a third protein, gasdermin D, which forms a pore in the plasma membrane that causes programmed lytic cell death, or pyroptosis. The function of caspase-1 in other cell types is now beginning to be studied, and these may be slightly different from its function in macrophages. In this regard, in IECs inflammasomes were recently shown to drive exfoliation of the compromised IEC, ejecting it into the gut lumen. Caspase-1 is the founding member of the larger caspase family. Caspases are normally considered as either apoptotic or inflammatory, however in recent years many interactions across classes have been demonstrated. Here we examine how IECs are defended by caspase-1, but also that other normally apoptotic caspases are also involved in exfoliation. We will study the innate immune inflammasome sensors that drive exfoliation during bacterial infection, and also how different innate immune cells coordinate their activities to promote IEC exfoliation.

抽象的许多细菌病原体试图粘附或侵入肠上皮细胞（IEC），经常使用操纵IEC中胞质信号通路的病毒因子。但是，IEC能够调查通过在炎症家族中使用先天免疫传感器，它们的细胞质。我们已经表明炎症体可以通过检测异常的易位来检测细菌分泌系统的活性细菌鞭毛蛋白，棒和针蛋白。炎症体在很大程度上是在巨噬细胞中研究的，在巨噬细胞中，首先证明了活性caspase-1 将pro-il-1β和pro-il-18清楚并释放形式。最近显示caspase-1清除第三个蛋白质，加油动物D，在质膜中形成孔，引起编程的裂解细胞死亡或凋亡。 caspase-1在其他单元类型中的功能现在开始研究，这些功能可能与巨噬细胞中的功能略有不同。在这方面，在IECS中，炎症是最近的证明可以驱动受损的IEC的去角质，并将其弹出到肠道内。 caspase-1是较大的caspase家族的创始成员。胱天蛋白酶通常被认为是凋亡或炎症性，但是近年来，各个班级的许多相互作用已经存在证明。在这里，我们检查了IEC如何通过caspase-1捍卫，但也通常是其他通常凋亡的胱天蛋白酶也参与去角质。我们将研究驱动驱动的先天免疫炎性体传感器在细菌感染期间去除角质，以及不同的先天免疫小球如何协调其活性促进IEC去角质。