Unmutated but T cell dependent IgM antibodies targeting Streptococcus suis play an essential role in bacterial clearance.

Autor: Dominic Dolbec, Mélanie Lehoux, Alexis Asselin de Beauville, Astrid Zahn, Javier Marcelo Di Noia, Mariela Segura
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: PLoS Pathogens, Vol 20, Iss 1, p e1011957 (2024)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
59639504
DOI: 10.1371/journal.ppat.1011957&type=printable
Popis: Streptococcus suis serotype 2 is an important encapsulated bacterial swine pathogen and zoonotic agent for which no effective vaccine exists. The interaction with B cells and the humoral response against S. suis are poorly understood despite their likely relevance for a potential vaccine. We evaluated germinal center (GC) B cell kinetics, as well as the production and role of S. suis-specific antibodies following infections in a mouse model. We found that mice infected with S. suis developed GC that peaked 13-21 days post-infection. GC further increased and persisted upon periodic reinfection that mimics real life conditions in swine farms. Anti-S. suis IgM and several IgG subclasses were produced, but antibodies against the S. suis capsular polysaccharide (CPS) were largely IgM. Interestingly, depletion of total IgG from the wild-type mice sera had no effect on bacterial killing by opsonophagocytosis in vitro. Somatic hypermutation and isotype switching were dispensable for controlling the infection or anti-CPS IgM production. However, T cell-deficient (Tcrb-/-) mice were unable to control bacteremia, produce optimal anti-CPS IgM titers, or elicit antibodies with opsonophagocytic activity. SAP deficiency, which prevents GC formation but not extrafollicular B cell responses, ablated anti S. suis-IgG production but maintained IgM production and eliminated the infection. In contrast, B cell deficient mice were unable to control bacteremia. Collectively, our results indicate that the antibody response plays a large role in immunity against S. suis, with GC-independent but T cell-dependent germline IgM being the major effective antibody specificities. Our results further highlight the importance IgM, and potentially anti-CPS antibodies, in clearing S. suis infections and provide insight for future development of S. suis vaccines.
Databáze: Directory of Open Access Journals
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