The lectin pathway of complement in pneumococcal infection

肺炎球菌感染中补体的凝集素途径

• 批准号: G0801952/1
• 负责人: Wilhelm Schwaeble
• 金额: $ 70.52万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801952%2F1
• 关键词: lectin; pathway; complement; pneumococcal; infection

This research proposal is based on a strong body of evidence demonstrating the prominent role of an only recently discovered effector arm of the immune system, termed the lectin pathway of complement, in fighting pneumococcal infections. Using an established model of experimental Streptococcus pneumoniae airway infection, the applicants observed that their gene-targeted mouse strain with a total deficiency of the lectin activation pathway is severely compromised in fighting S. pneumoniae infection resulting in a dramatic increase in the severity of pneumococcal disease and mortality, compared to mice with an intact lectin activation pathway. The proposed research aims to define the key components and biochemical mechanisms involved in lectin pathway mediated protection from invasive pneumococcal infection within the immune defense. The availability of a unique combination of mouse strains deficient of either single or several components of the lectin pathway is essential to define the key players in anti-pneumococcal immunity using in vivo models of infection. The in vivo work is supported by an array of sophisticated biochemical analyses using recombinant proteins generated in cell lines to reconstitute and measure lectin pathway functional activity in a test tube. The work programme will also include the analysis of a molecular mechanism used by pathogenic S. pneumoniae strains to evade from the attack of its host s complement system and may explain the essential role of the lectin pathway activation route in fighting infection with these strains. The results of this work programme will have wide implications for the understanding of predispositions to human pneumococcal disease.

该研究建议基于大量证据，证明了免疫系统的唯一一个最近发现的效应子的重要作用，称为补体的凝集素途径在抗击肺炎球菌感染中。使用既定的实验性肺炎肺炎气道感染模型，申请人观察到，其基因靶向的小鼠菌株完全缺乏凝集素激活途径在与肺炎链球菌疾病疾病疾病疗法的急剧促进性促进性促进性肺炎链球菌感染时严重妥协，与鼠标疾病疗法相比，与鼠标促进了菌丝的症状急剧增加。拟议的研究旨在定义参与凝集素途径涉及的关键成分和生化机制，介导了免疫防御内侵入性肺炎球菌感染的保护。使用凝集素途径的单个或几个成分的小鼠应变的独特组合对于使用体内感染模型来定义抗波经菌免疫的关键参与者至关重要。体内工作得到了一系列复杂的生化分析的支持，该分析使用细胞系中产生的重组蛋白来重建和测量试管中的凝集素途径功能活性。该工作计划还将包括对肺炎链球菌菌株使用的分子机制的分析，以逃避其宿主补体系统的攻击，并可以解释凝集素途径激活途径在用这些菌株对抗感染中的基本作用。该工作计划的结果将对对人肺炎球菌疾病的易感性的理解具有广泛的影响。