Fig. 2. Examples of microbiota influence on the adaptive immune responses.

Signals from commensal bacteria induce production of BAFF, APRIL and TGF-β in the intestinal epithelial cells (IEC) and dendritic cells (DC), which in turn promotes the differentiation of B cells into IgA⁺ plasma cells. After activation by commensal bacteria follicular dendritic cells (FDC) also promote the differentiation of B cells into IgA⁺ plasma cells, as they are a main producers of TGF-β in the Payer’s patches. Commensals can regulate function of the innate lymphoid cells (ILC) which in turn promote T cell independent IgA induction through the interaction of membrane bound lymphotoxin (LTα₁β₂) with DC, whereas soluble form of ILC-derived lymphotoxin (sLTα₃) supports T cell dependent IgA induction by promoting T cell homing to the lamina propria, presumably influencing Tfh population. Segmented filamentous bacteria (SFB) are found in close contact with IEC where they may induce SAA that stimulates DC and promotes the differentiation of Th17 cells. Presentation of SFB antigens by DC on MHC II is also needed for Th17 induction. Microbiota derived signals induce IL-1β production by mononuclear phagocytes that promotes Th17 differentiation. ATP produced by certain commensals activates DCs and leads to induction of Th17 cells. Th17 cells can differentiate into Tfh cell and therefore contribute to IgA production. Polysaccharide A (PSA) produced by Bacteroides fragilis directly promotes Treg cell differentiation via TLR2 or indirectly by conditioning DCs. Microbiota derived short chain fatty acids (SCFA), a by-product of metabolism, may promote Treg cell generation either directly through signalling via GPCR43 or indirectly via IEC. Clostridium species belonging to clusters IV, XIVa and XVIII induce TGF-β production in IEC, which promotes Treg differentiation in the colon.