Recognition of the microbiota by the adaptive immune system is dependent on the uptake and intracellular transport of organisms by local dendritic cells that remain in Peyer’s patches or migrate no further than the mesenteric lymph node (see Fig. 12.21), which acts to prevent wider dissemination of the microbiota. Because commensal microbes are noninvasive, dendritic cells are not fully activated and induce a finely balanced response, comprising secretory IgA antibodies that enter intestinal secretions and are directed at commensal bacteria. Up to 75% of commensal organisms living in the lumen appear to be coated by IgA (see Fig. 12.21), limiting their adherence to and penetration of the epithelium. In addition, coating of the microbiota with SIgA can alter their gene expression. Many of the large numbers of fully differentiated TH1 and
Fig. 12.20 Infection by Clostridium difficile. Treatment with antibiotics causes massive death of the commensal bacteria that normally colonize the colon. This allows pathogenic bacteria to proliferate and to occupy an ecological niche that is normally occupied by harmless commensal bacteria. Clostridium difficile is an example of a pathogen producing toxins that can cause severe bloody diarrhea in patients treated with antibiotics.
Fig. 12.21 Several local processes ensure peaceful homeostasis between host and microbiota. Commensal bacteria in the lumen gain access to the immune system via M cells. Antigens are taken up by dendritic cells in Peyer’s patches and isolated follicles under noninflammatory conditions (left panel). Presentation of these antigens generates IgA‑switched B cells that localize in the lamina propria as IgA‑producing plasma cells (right panel). IgA then binds commensal bacteria, altering their gene expression, limiting their access to the epithelium, and blocking their binding to the surface. Interference with penetration of the epithelium is assisted by the presence of thick layers of mucus, which also contain mucin glycoproteins that have antibacterial properties. In addition, stimulation of pattern recognition receptors on Paneth cells induces the production of antimicrobial peptides such as RegIIIγ and defensins (see Section 2‑4), which are also stimulated by IL‑22 derived from TH17 CD4 T cells and ILC3s. IL‑22 also tightens the epithelial barrier. Phagocytic macrophages found immediately under the epithelium can ingest and kill bacteria that penetrate the surface.
TH17 cells found in healthy intestine are also directed at the microbiota. While these cells produce mediators that can assist bacterial clearance by macrophages and epithelial cells, they come with the risk of producing inflammation and collateral damage. This does not occur, because of IL-10 produced by T cells and FoxP3+ regulatory T cells present in the mucosa. TH17 and FoxP3+ regulatory T cells in the intestine can enter germinal centers in Peyer’s patches and acquire the functions of follicular helper T cells, leading to selective IgA switching.