Porcine jejunal Peyer’s patches leukocytes are a potent source of mucosal IgA binding to Streptococcus suis and suilysin

Abstract Human Streptococcus suis infections are frequently linked to undercooked pork consumption, particularly in Southeast Asia. Experimental evidence indicates that S. suis can cross the intestinal barrier and cause systemic infection in pigs, suggesting the gut as a plausible entry site. However, mucosal immunity against S. suis in the intestinal tract remains poorly characterized. Here, we provide initial insights into the intestinal source and production of mucosal IgA against S. suis in 8-week-old conventional pigs. We show that jejunal and ileal mucus contains IgA recognizing a commensal S. suis isolate as well as a virulent S. suis cps 2 strain. Mucosal IgA antibodies also bind to the secreted virulence-associated protein suilysin (SLY). Flow cytometric analysis of porcine Peyer’s patches (PP) leukocytes of the jejunum (JPP) and the ileum (IPP) revealed a significantly higher frequency of IgA + B cells in JPP. Moreover, JPP-derived leukocytes showed higher constitutive and stimulation-induced total IgA secretion than IPP-derived leukocytes. Stimulation, either with the T cell-associated factors CD40L and IL-21 or the TLR1/2 ligand Pam3Cys-SK4 induced anti- S. suis IgA secretion, particularly in JPP-derived leukocyte cultures, indicating a contribution of innate immune mechanisms and an important role for T cell help. Finally, IgA induced by in vitro stimulation of JPP- or IPP-derived leukocytes recognized commensal and virulent S. suis as well as SLY, involved in disrupting epithelial barriers. Our results suggest that S. suis elicits a mucosal immune response in the intestinal tract of conventional piglets, with B cells in JPP representing a key site of IgA production.