Differences in the cell-wall architecture drive strain-specific IgA induction by <i>Limosilactobacillus reuteri</i>

Limosilactobacillus reuteri (formerly Lactobacillus reuteri) is a well-studied commensal bacterium known for various health benefits. 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 between the human isolates CF48-3A and PTA-6475, we observed that only CF48-3A induces splenocyte IgA production in vitro, highlighting strain-specific functional diversity within L. reuteri. Further study revealed 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 IgA+ plasmablast differentiation and proliferation, PTA-6475 fails to promote antibody-secreting cell populations and does not induce IgA. This latter phenotype was traced to differences in the cell surface architecture. A derivative of PTA-6475 in which eight genes encoding cell surface proteins were inactivated (L. reuteri VPL4366) gained the function to promote plasmablast differentiation and IgA induction. Additionally, IgA induction by CF48-3A and L. reuteri VPL4366 appears to occur, at least partially, via TLR2 signaling, and is not associated with B lymphocyte stimulator (BLyS) or TGF-β signaling. These in vitro findings emphasize the strain-specific cell wall architecture plausibly impacts L. reuteri on IgA induction and suggest unique mechanisms by which L. reuteri strains influence B cell differentiation.