Salmonella-Induced Changes in Immunoregulatory Bacteria and the Impact on Transcriptional Activity of the Foxp3 and Roryt genes in Rat GALT

Abstract

Intestinal microbiome supports immune homeostasis. Segmental filamentous bacteria (SFB) induce differentiation of Th17-cells in enteric-associated lymphoid tissue (GALT). Clostridium (cluster IV and XIVa) and Bacteroidesfragilis (polysaccharide A) stimulate the formation of T-regulatory cells (Treg) and production of suppressor cytokine IL-10. METHODS: Metabolites of B. fragilis, short-chain fatty acids (SCFA), activate GALT cells through the FFAR2 receptor. Decrease in the concentration of SCFA decreases the number of Treg and disrupts the balance of Th17/Treg, which leads decreased level of FFAR2, Foxp3 mRNA and an increase in RORgt in GALT. Vancomycin and salmonella were given to rats and the levels of SFB assessed. RESULTS: SFB increased and A.muciniphila, F.prausnitzii decreased post Vancomycin and salmmonella. In rats infected with salmonella after pretreatment with vancomycin, the number of SFBs increased with a marked decrease in the Bacteroides-Prevotela group, A.muciniphila, Clostridium spp. clusters XIV, IV, and F.prausnitzii, leading to a decrease in the expression level of Foxp3 + gene mRNA and an increase in Rorgt +. The introduction of B. fragilis to animals receiving Salmonella on the background of pre-treatment with vancomycin caused a decrease in the level of SFB and mRNA of Rorgt +, and, conversely, increased the number of Bacteroides-Prevotela group, A.muciniphila, Clostridium spp. clusters XIV, IV, F.prausnitzii and expression of Foxp3 + genes, indicative of restoration of intestinal microbiome homeostasis. CONCLUSIONS: Salmonella-induced changes in immunoregulatory bacteria impacts transcriptional activity of the Foxp3 and Roryt genes in rat GALT.