SCAVENGER RECEPTOR FUNCTION IN CHAPERONE-ELICITED ADAPTIVE IMMUNE RESPONSES

伴侣引发的适应性免疫反应中的清道夫受体功能

• 批准号: 7959992
• 负责人: Brent L Berwin
• 金额: $ 15.99万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959992
• 关键词: A Mouse; Antigen-Presenting Cells; Bacteria; Bacterial Infections; Computer Retrieval of Information on Scientific Projects Database; Data; Dendritic Cells; Escherichia coli; Funding; Gram-Negative Bacteria; Grant; Immune response; Institution; Investigation; Leukocytes; Ligands; Malignant neoplasm of ovary; Mediating; Molecular; Molecular Chaperones; Pathogenesis; Pattern recognition receptor; Pseudomonas aeruginosa; Publishing; Research; Research Personnel; Resources; Role; Source; Toll-like receptors; United States National Institutes of Health; abstracting; base; cystic fibrosis patients; microbial; novel; pathogen; receptor; receptor binding; receptor function; scavenger receptor; trafficking

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Scavenger receptors are pattern recognition receptors that bind and traffic a variety of endogenous and microbial ligands. The broad objective of our current studies is to define the mechanisms by which scavenger receptors modulate, and can be targeted to modulate, immune responses from leukocytes. Specifically, we are investigating: 1) how Scavenger Receptor Class-A (SR-A) functions to internalize bacteria and chaperones into antigen-presenting cells, and 2) how SR-A -expressing leukocytes contribute to ovarian cancer. A large part of our effort is directed towards Aim 1, which evokes from our identification of SR-A as a novel endocytic receptor for the molecular chaperones gp96 and CRT. With the use of SR-A-/- mice we have focused on elucidating the mechanisms by which scavenger receptors mediate the immunological effects of chaperones. Recent data on this project were published in Bak et al. (2008) and Tewalt et al. (2008). Our studies have recently expanded to identify the role of SR-A during bacterial infection with the use of dendritic cells (DCs) from SR-A-/- mice. Functional analyses elucidated a novel interplay between SR-A and the Toll-like receptors (TLR) for DC internalization of the gram-negative bacteria E. coli (Amiel et al., 2009). Current efforts are now directed at extending these investigations to the bacteria Pseudomonas aeruginosa, which is a bacterial pathogen that substantially contributes to the pathogenesis of cystic fibrosis (CF) patients. The COBRE-funded studies described in this Abstract formed the basis for our subsequently-funded NIH RO1 grant.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 清道夫受体是结合和运输多种内源性和微生物配体的模式识别受体。我们目前研究的主要目的是确定清道夫受体调节白细胞免疫应答的机制，并可靶向调节白细胞免疫应答。具体来说，我们正在研究：1）清道夫受体A类（SR-A）如何将细菌和伴侣内化到抗原呈递细胞中，以及2）表达SR-A的白细胞如何促进卵巢癌。 我们的努力的很大一部分是针对目标1，这引起了我们的鉴定SR-A作为一种新的内吞受体的分子伴侣gp 96和CRT。随着SR-A-/-小鼠的使用，我们集中在阐明清道夫受体介导的伴侣蛋白的免疫学效应的机制。关于该项目的最新数据发表在巴克等人（2008年）和Tewalt等人（2008年）。我们的研究最近扩大到确定SR-A在细菌感染过程中的作用，使用来自SR-A-/-小鼠的树突状细胞（DC）。功能分析阐明了SR-A和Toll样受体（TLR）在革兰氏阴性菌E.大肠杆菌（Amiel等人，2009年）。目前的努力是针对这些调查的细菌铜绿假单胞菌，这是一种细菌病原体，大大有助于囊性纤维化（CF）患者的发病机制。本摘要中描述的COBRE-funded研究构成了我们自愿资助的NIH RO 1资助的基础。