Strain-specific modulation of IgA induction by Limosilactobacillus reuteri 2310

Description Limosilactobacillus reuteri (formerly Lactobacillus reuteri) is a well-studied commensal bacterium known for various health benefits, although recent evidence links specific strains to autoimmune conditions. Our recent findings reveal that the human-derived strain L. reuteri CF48-3A enhances endogenous neonatal immunoglobulin A (IgA) production in mice. In a comparative analysis of CF48-3A and ATCC PTA 6475, we observed that only CF48-3A induces splenic IgA production in vitro, highlighting strain specific functional diversity within L.reuteri. Further study indicates that the two strains modulate B cell IgA production through distinct mechanisms, largely due to differences in surface proteins and activation of Toll-like receptor 2 (TLR2). While CF48-3A promotes plasmablast differentiation and proliferation, PTA 6475 does not induce IgA production and suppresses antibody-secreting cell populations. This suppression was traced to differences in surface architecture, as knockout of Sortase A (SrtA)-dependent proteins (SDPs), responsible for anchoring proteins to the cell surface, restored plasmablast differentiation and IgA induction in PTA 6475. Additionally, IgA induction by CF48-3A and the SDPs mutant PTA 6475 appears to occur independently of BAFF and TGF-β signaling. These findings emphasize the strain-specific impact of L. reuteri on IgA induction and suggest unique mechanisms by which L. reuteri strains influence B cell differentiation. Funding Sources Supported by NIH UL1TR003015 Topic Categories Mucosal and Regional Immunology (MUC)