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

当免疫系统未能对入侵的病原体做出最佳反应时，通常会发生感染。因此，操纵免疫系统以产生对病原体的有效免疫力的探索可以被视为现代免疫学的重大挑战。协调这种免疫的一个不可或缺的因素是一种罕见但分布广泛的细胞网络，称为树突状细胞(DC)。DC表达病原体识别受体，以感知微生物或疫苗并对其做出反应。过去十年的研究表明，树突状细胞在启动和控制免疫反应的质量和强度方面发挥着重要作用。然而，关于DC在对胞外细菌的免疫反应中所起作用的信息很少，其中大部分被一层糖壳覆盖，称为多糖囊(CPS)，帮助细菌躲避免疫系统。这些可怕细菌的两个例子是B组链球菌(GBS)，它是新生儿和孕妇疾病和死亡的主要原因；以及猪链球菌，世界范围内的一种重要的猪病原体，可以传播给人类。这两种病原体都会导致严重的侵袭性疾病。在我的研究计划中，我建议描绘GBS和猪链球菌与DC和其他免疫细胞的相互作用，以确定DC可以通过哪些机制克服被包裹的细菌逃避免疫系统的策略，从而启动保护性免疫反应。这些研究的数据将为微囊化细菌引起的疾病的发病机制提供新的见解，从而有助于推动针对这些重要病原体的控制措施的发展。

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.