Figure 1.

Microbiota–T cell crosstalk in the maintenance of gut homeostasis. Commensal bacteria can trigger pattern recognition receptors (PPRs) on enterocytes and/or activate antigen specific CD4+T cell responses via dendritic cells (DC). Naïve CD4+ T cells can differentiate into four major cell types: Th1, Th2, Th17 and Tregs. The differentiation of each Th type requires specific transcription factors and cytokine sets, as shown in the figure. Th1 cells play an important role in eliminating intracellular pathogens while Th2 control parasitic infections and extracellular pathogens trough the induction of antibody responses. The primary role of Th17 cells is to control infection, but also contributes to intestinal homeostasis by inducing protective IgA responses. SFB commensal bacteria promote gut Th17 cell responses by triggering the intestinal production of SAA and ROS. iTreg cells play a key role in controlling Th cell responses and in maintaining gut immune homeostasis. Several commensal bacteria such as Clostridia spp., dietary compounds (SCFA) and AhR ligands participate in the maintenance of tolerance by inducing gut Treg cell responses or by imprinting tolerogenic features on DCs, as is the case for Alcaligenes spp. Other immune cell types such as invariant natural killer T-cells (iNKT) are suppressed and controlled by bacterial sphingolipids preventing intestinal pro-inflammatory responses. In addition, type 3 innate lymphoid cells (ILC3) promote protective Th17 responses via IL-22 and IL-17. The types of bacteria implicated in particular T cell differentiation pathways as well as metabolites are indicated in the figure. SFB, segmented filamentous bacteria; AhR, Aryl hydrocarbon receptor; TGF-β, transforming growth factor-beta; SCFA, short-chain fatty acids; PSA, polysaccharide A; SAA, serum amyloid A protein; ROS, reactive oxygen species; GALT, gut-associated lymphoid tissue; TSLP, thymic stromal lymphopoietin; iTreg, induced regulatory T cell.