Regulation of Host Immunity by the Gut Microbiota

Constant exposure to diverse microorganisms has accompanied human evolution and continues to shape immunological development throughout life. In mucosal tissues, both innate and adaptive arms of the immune system are required to support healthy mutualistic interactions with the resident microbiota, while aggressively fighting pathogenic infections. Technological breakthroughs over the past decade facilitated groundbreaking discoveries that transformed our understanding of intestinal immunology and established the gut microbiota as a critical factor that shapes immunological development and function. Indeed, alterations to microbiota composition (dysbiosis) are associated with a wide array of human diseases, including autoimmune diseases, chronic inflammation, the metabolic syndrome, and cancer. In this chapter, we discuss fundamental concepts that underlie microbiota-immune system crosstalks, and their subsequent impact on host immunity, in health and disease. Given the widespread scope of this growing research field, we focus primarily on adaptive immune responses induced by the gut microbiota and mediated by intestinal effector and regulatory T cells. We further highlight non-immune cellular components that facilitate homeostatic host-microbiota communications in the gut. Finally, we discuss how disruptions to microbiota-immune system interactions provoke inflammatory responses in the gut and beyond and propose that rationally designed microbiota-based therapy may serve as an innovative avenue for future therapeutics.