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

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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.