甲酰肽受体的免疫识别和炎症调控机制研究

项目名称： 甲酰肽受体的免疫识别和炎症调控机制研究

项目编号： No.31470865

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 免疫学

项目作者： 叶德全

作者单位： 上海交通大学

项目金额： 80万元

中文摘要： 原核细胞如细菌的蛋白质合成起始于带甲酰肽的甲硫氨酸，这一特征成为哺乳动物免疫细胞识别细菌的一个有效标志。免疫细胞利用其专门识别甲酰肽的受体（FPR），发现并追踪入侵的细菌并将其杀灭。本项目在前期工作的基础上，旨在通过对甲酰肽受体的进一步研究，揭示天然免疫细胞识别入侵细菌的一种机制，阐明甲酰肽受体在调控抗感染免疫和炎症反应中的生理病理功能。本项目将要解答如下科学问题：（1）甲酰肽受体能否鉴别致病菌和非致病菌并产生不同的宿主细胞反应？（2）甲酰肽受体如何识别多种化学性质和结构截然不同的配体？（3）甲酰肽受体如何转导致炎和抗炎两种的不同信号？主要研究内容分为两大部分，即甲酰肽受体对配体的识别机制和甲酰肽受体的信号转导机制。我们拟运用受体药理学、分子生物学、微生物和免疫学等学科知识以及相应的实验手段，通过对这一类受体的深入研究，了解免疫细胞识别细菌等入侵微生物的机制，为基础研究成果的转化应用奠定基

中文关键词： 免疫细胞；信号转导；炎症反应；分子生物学

英文摘要： Protein synthesis in prokaryotic cells such as bacteria starts with an N-formyl methionine (N-fMet), a feature that is utilized by mammalian immune cells for the identification of invading bacteria. Immune cells use specialized receptors that recognize N-formyl peptides (the formyl peptide receptors, FPR) to identify and capture invading bacteria, leading to its eventual elimination. Based on our preliminary results, we propose to conduct an in-depth study of the FPRs for a better understanding of the mechanisms by which FPRs detect bacteria and of their patho-physiological functions in the regulation of anti-infection immunity and inflammatory response. This proposal aims to address the following scientific questions: (1) Can FPRs distinguish between pathogenic bacteria from non-pathogenic bacteria and mount different host responses? (2) How do the FPRs bind diverse ligands of different chemical structures? (3) How do the FPRs transducer both pro-inflammatory and anti-inflammatory signals? The proposed research is divided into two parts, namely the recognition mechanisms used by the FPRs and their signal transduction mechanisms. We propose to use knowledge of receptor pharmacology, molecular biology, microbiology and immunology, as well as related experimental procedures, to study FPRs and gain a better understanding of the mechanisms by which host cells detect invading microorganisms. Our long-term goal is to translate basic research results into clinically useful applications.

英文关键词： Immune cells;Signal transduction;Inflammation;Molecular biology