Dendritic cell interactions with capsular polysaccharides from pathogenic streptococci: impact on innate and adaptive immune responses

树突状细胞与致病性链球菌荚膜多糖的相互作用：对先天性和适应性免疫反应的影响

• 批准号: 342150-2013
• 负责人: Segura, Mariela
• 金额: $ 3.64万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572464
• 关键词: Dendritic; cell; interactions; capsular; polysaccharides

Infection often occurs when the immune system fails to respond optimally to invading pathogens. Therefore, the quest to manipulate the immune system to generate effective immunity against pathogens can be considered as the 'grand challenge' of modern immunology. An integral player orchestrating this immunity is a rare but widely distributed network of cells called dendritic cells (DCs). DCs express pathogen recognition receptors to sense and respond to microbes or vaccines. Research in the last decade has shown a fundamental role for DCs in initiating and controlling the quality and strength of the immune response. However, little information is available regarding the role of DCs in the immune response to extracellular bacteria, most of which are covered by a shell of sugars, known as the polysaccharide capsule (CPS), that help bacteria hiding from the immune system. Two examples of these redoubtable bacteria are Group B Streptococcus (GBS), which is a leading cause of disease and mortality in newborns and pregnant women; and Streptococcus suis, an important swine pathogen worldwide, which can be transmitted to humans. Both pathogens cause severe invasive diseases. In my research plan, I propose to delineate the interactions of GBS and S. suis with DCs and other immune cells to identify mechanisms by which DCs can overcome the strategies used by encapsulated bacteria to evade the immune system and thus initiate a protective immune response. Data from these studies will provide new insights into the pathogenesis of the disease caused by encapsulated bacteria, thereby helping to advance the development of control measures against these important pathogens.

感染通常发生在免疫系统无法对入侵的病原体做出最佳反应时。因此，操纵免疫系统以产生针对病原体的有效免疫的探索可以被认为是现代免疫学的“重大挑战”。协调这种免疫的一个不可或缺的参与者是一种罕见但广泛分布的细胞网络，称为树突状细胞（DC）。树突状细胞表达病原体识别受体，对微生物或疫苗进行感知和应答。过去十年的研究表明，DC在启动和控制免疫应答的质量和强度方面发挥着重要作用。然而，关于DC在对细胞外细菌的免疫应答中的作用的信息很少，其中大部分被称为多糖胶囊（CPS）的糖壳覆盖，这有助于细菌躲避免疫系统。这些可怕的细菌的两个例子是B族链球菌（GBS），这是新生儿和孕妇疾病和死亡的主要原因;和猪链球菌，世界范围内的一种重要的猪病原体，可以传播给人类。这两种病原体都会引起严重的侵袭性疾病。在我的研究计划中，我建议描述GBS和S的相互作用。猪与DCs和其他免疫细胞，以确定DCs可以克服包囊细菌逃避免疫系统所使用的策略，从而启动保护性免疫应答的机制。这些研究的数据将为包囊细菌引起的疾病的发病机制提供新的见解，从而有助于推进针对这些重要病原体的控制措施的发展。