Microbial control of regulatory and effector T cell responses in the gut

Abstract

The human intestine harbors and is in constant contact with 1000 trillion microbes, composed of an estimated 15,000 strains. Recent studies have changed our perspective of commensal microbes from benign but inert passengers, to active participants in the processing of food into useful metabolic components, the postnatal development of mucosal and systemic immunity, and in its long-term steady state function. Although mucosal surfaces have to constitutively integrate a multitude of microbial derived signals, new evidence suggests that defined bacteria or microbial products can play a dominant role in the induction of distinct class of immune responses. In this review we will focus on recent findings associating microbes that colonize or invade the gut, specialized mucosal DCs, and induction of effector or regulatory response in the GI tract.

Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota

“…Inflammatory CD4 + RORgt + T cells as well as anti-inflammatory CD4 + Foxp3 + T cells are critical in maintaining homeostasis in the gut (Hand and Belkaid, 2010). In contrast to MMb, SFB monocolonization only partially expanded CD4 + RORgt + T cells (Figures 6D andS6F) and failed to increase CD4 + Foxp3 + cell numbers in PPs (Figure 6E).…”

Central Nervous System Demyelinating Disease Protection by the Human Commensal Bacteroides fragilis Depends on Polysaccharide A Expression

“…Gut commensal microorganisms can modulate immune homeostasis (6)(7)(8)(9)(10)(11)(12)(13). Studies in germ-free animals, born and raised in sterile conditions, showed that monocolonization with Bacteroides fragilis was sufficient to stimulate early development of the GALT, to induce normal organogenesis in the spleen and thymus, and balanced immune development (14).…”

Experimental Inflammatory Bowel Disease: Insights into the Host-Microbiota Dialog

“…Our co-existence with the microbiota is a dynamic and mutually beneficial one. In addition to a profound influence on host metabolism (Backhed et al, 2004; Backhed et al, 2005) and intestinal development, the commensal flora shapes the immune system both at mucosal surfaces (Hand and Belkaid, 2010; Rescigno, 2009) and systemically (Clarke et al, 2010), and actively protects from enteric pathogenic infections by colonization resistance and by synthesizing factors promoting mutualism. For instance, polysaccharide A produced by Bacteroides fragilis suppresses IL-17 production in the intestine and promotes the function of IL-10-producing CD4 + T cells, which confers protection in an experimental model of colitis induced by Helicobacter hepaticus (Mazmanian et al, 2008).…”