Identification of essential genes and receptors for the signaling of TLR2-dependent bacterial virulence factors (lipopeptides, peptidoglycan and lipoteichoic acid)

鉴定 TLR2 依赖性细菌毒力因子（脂肽、肽聚糖和脂磷壁酸）信号转导的必需基因和受体

• 批准号: 5357091
• 负责人: Professor Dr. Holger Heine
• 金额: --
• 依托单位: Programmbereich Chronische Lungenerkrankungen
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2003-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5357091?language=en
• 关键词: Identification; essential; genes; receptors; signaling

The recognition of bacterial virulence factors by the innate immune system is the first step in mounting an adequate immune response that eventually will clear the host from the invading pathogen. The molecular basis for this recognition has just recently started to be understood. Components of Gram-negative and -positive bacteria cell walls, such as lipopolysaccharides (LPS), lipopeptides/lipoproteins (LP), peptidoglycan (PG), and lipoteichoic acid (LTA) are very potent activators of innate immune responses. Their main target cells are monocytes and the primary host recognition of some of these components is mediated through CD14. However, recent data show obvious differences between the mediating signaling receptors and pathways of LPS and LP/PG/LTA. Whereas LPS-responsive cells express Toll-like receptor (TLR) 4, LP/PG/LTA require the expression of TLR2. Furthermore, data are emerging that clearly favor the engagement of multimeric receptor complexes by bacterial pathogens. This project will focus on investigating the recognition and signaling of the TLR2-dependent bacterial virulence factors LP/PG/LTA. The aims of this project are 1) the identification and characterization of so far unknown genes that are essential for the signaling of LP/PG/LTA and 2) the analysis of the receptor complexes mediating LP/PG/LTA recognition.

先天免疫系统对细菌毒力因子的识别是建立充分免疫反应的第一步，最终将清除入侵病原体的宿主。这种认知的分子基础最近才开始被理解。革兰氏阴性和阳性细菌细胞壁的成分，如脂多糖（LPS）、脂肽/脂蛋白（LP）、肽聚糖（PG）和脂质胆酸（LTA）是先天免疫反应的非常有效的激活剂。它们的主要靶细胞是单核细胞，其中一些成分的主要宿主识别是通过CD14介导的。然而，最近的数据显示，LPS和LP/PG/LTA介导的信号受体和通路存在明显差异。lps应答细胞表达toll样受体（TLR） 4， LP/PG/LTA则需要TLR2的表达。此外，正在出现的数据清楚地支持多聚体受体复合物与细菌病原体的接触。本项目将重点研究tlr2依赖性细菌毒力因子LP/PG/LTA的识别和信号转导。本项目的目的是1)鉴定和表征迄今为止未知的对LP/PG/LTA信号传导至关重要的基因，2)分析介导LP/PG/LTA识别的受体复合物。