The endotoxin present on commensal bacteria also seems unusually sensitive to neutralization by gut enzymes such as alkaline phosphatase, leading to weaker immune activation. If commensal bacteria do cross the epithelium in small numbers, their lack of virulence factors means they cannot resist uptake and killing by phagocytic cells, and they are rapidly destroyed. In contrast to what happens in other tissues, ingestion of commensal bacteria in the intestine does not lead to inflammation. If macrophages cannot respond to the inhibitory effects of IL-10, intestinal inflammation develops spontaneously. Eosinophils in the healthy intestine assist antigen-specific IgA switching by producing APRIL, IL-6, and TGF-β when exposed to commensal microbes (see Section 12-11). Thus, commensal organisms associate with the mucosal surface without invading or provoking inflammation. This symbiosis involves many innate and adaptive immune effector cells that are usually associated with chronic inflammation but in the intestine create a state sometimes referred to as physiological inflammation.
12-21 The intestinal microbiota plays a major role in shaping intestinal and systemic immune function.
Commensal bacteria and their products play an essential role in normal development of the immune system. This effect is illustrated in germ-free, or gnotobiotic, mice, in which there is no colonization of the gut by microorganisms. These animals have marked reductions in the size of all lymphoid organs, low serum immunoglobulin levels, fewer mature T cells, and markedly reduced immune responses, especially TH1 and TH17 responses. Such mice are prone to make TH2-type responses such as IgE antibodies and are more susceptible
Fig 12.22 Effects of the microbiota on disease and systemic immune function.
The presence and composition of the microbiota have many downstream consequences for the function of the immune system and other body tissues, some of which may be secondary to the events in the mucosa, while others may reflect the ability of products of intestinal microbes to enter the circulation. The microbiota is also known to have many effects on susceptibility to a wide range of diseases in humans and experimental animals.
to certain immunological diseases such as type 1 diabetes. In the intestine, Peyer’s patches do not develop normally and isolated lymphoid follicles are absent. Germ-free mice also have severely reduced numbers of T lymphocytes and ILCs in the lamina propria and epithelium, nearly absent IgA-secreting plasma cells, and reduced mediators of local immunity, such as antimicrobial peptides, retinoic acid, IL-7, IL-22, IL-25, IL-33, and TSLP. In contrast, invariant NKT cells (iNKTs) are more abundant in the germ-free intestine, perhaps contributing to the TH2 bias seen in germ-free animals.