The structure-function relationships between capsular polysaccharides and the immune system during Streptococcus suis infections

猪链球菌感染过程中荚膜多糖与免疫系统的结构-功能关系

• 批准号: RGPIN-2021-03020
• 负责人: Segura, Mariela
• 金额: $ 4.23万
• 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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742335
• 关键词: structure; function; relationships; between; capsular

The compulsory reduction in livestock antibiotic use and lack of vaccines have led to the re-emergence of bacterial pathogens responsible for significant economic loss and a surge in animal welfare concerns, particularly in the swine industry. Among these pathogens, encapsulated bacteria are challenging due to the camouflage conferred by their capsular polysaccharide (CPS), which cloaks antigenic proteins on the bacterial surface that would otherwise trigger a protective immune response. The encapsulated bacterium Streptococcus suis (S. suis) has been classified as one of the swine industry's high-priority bacterial species based on the need for intervention tools. Due to the CPS, S. suis is generally highly resistant to phagocytic clearance, except in the presence of opsonizing antibodies, which facilitate bacterial elimination. Even so, the development of adaptive (humoral) immunity during S. suis infection is still poorly understood and thus translates into a lack of commercial vaccines to fight this disease in pigs. During the adaptive immune response, B cells are activated through antigen engagement, and T cell help. Together with somatic hypermutation and class-switch recombination, B cell clonal expansion in germinal centers mediate final antibody response fitness. Besides this classical T cell-dependent mechanism, antibody responses can emerge from T cell-independent pathways, especially those directed against the CPS. In the context of S. suis, these aspects are largely unknown. Furthermore, based on current knowledge on S. suis CPS serotypes and their behaviours, divergent B cell responses are expected. The general hypothesis is that encapsulated S. suis infections modulate the development of the adaptive immune response to the pathogen. Moreover, the role of S. suis CPSs differs between serotypes, and this feature impacts the dynamics and functionality of the antibody response. Building on our expertise, the general aim is to dissect the molecular and cellular pathways involved in the humoral adaptive immune response to encapsulated S. suis. Different methods will be used to understand how encapsulated S. suis modulates B cell activation and, consequently, antibody diversification. Molecular studies of the dynamic landscape in blood/tissues of infected/immunized animals will be combined with FACS analyses to provide a mechanistic understanding of B cell activation. Selected conditions will be used to evaluate the influence of the CPS type on the humoral response. We will characterize the antibody response and biological properties of induced antibodies. This program will generate fundamental knowledge on the immune response to encapsulated organisms and their carbohydrates, as well as provide a mechanistic understanding to design future vaccine strategies against S. suis - a development that is of utmost significance for swine production systems aiming to reduce antimicrobial use.

强制减少牲畜抗生素的使用和缺乏疫苗导致细菌病原体的重新出现，造成重大经济损失和动物福利问题的激增，特别是在养猪业。在这些病原体中，包囊细菌具有挑战性，因为它们的荚膜多糖（CPS）赋予了伪装，它掩盖了细菌表面的抗原蛋白，否则会引发保护性免疫反应。猪链球菌（Streptococcus suis，S. suis）已被归类为养猪业的高优先级细菌物种之一，这是基于对干预工具的需要。由于CPS，S。除了在存在调理抗体的情况下，SUIS通常对吞噬清除具有高度抗性，调理抗体促进细菌消除。即便如此，适应性（体液）免疫的发展在S。对猪流感的感染仍然知之甚少，因此缺乏在猪中对抗这种疾病的商业疫苗。 在适应性免疫应答期间，B细胞通过抗原接合被激活，并且T细胞帮助。与体细胞超突变和类别转换重组一起，B细胞在生殖中心的克隆扩增介导最终抗体应答适应性。除了这种经典的T细胞依赖性机制之外，抗体应答还可以来自T细胞非依赖性途径，特别是那些针对CPS的途径。在S.这些方面在很大程度上是未知的。此外，根据目前对S.猪CPS血清型和它们的行为，预期不同的B细胞应答。一般的假设是，封装S。猪感染调节对病原体的适应性免疫应答的发展。此外，S.猪CPS在血清型之间不同，并且该特征影响抗体应答的动力学和功能性。基于我们的专业知识，总的目标是剖析参与对包囊S的体液适应性免疫应答的分子和细胞途径。猪。 将使用不同的方法来理解如何封装S。猪调节B细胞活化，从而调节抗体多样化。感染/免疫动物血液/组织中动态景观的分子研究将与FACS分析相结合，以提供对B细胞活化的机制理解。选择的条件将用于评价CPS类型对体液应答的影响。我们将描述抗体反应和诱导抗体的生物学特性。该计划将产生对包囊生物及其碳水化合物的免疫应答的基础知识，并为设计未来的疫苗策略提供机械理解。suis -这是一项对旨在减少抗菌剂使用的养猪生产系统具有极其重要意义的发展。