Abstract
The intestinal mucosa is constantly exposed to a large number of commensal bacteria and challenged by pathogens. Consequently, the intestinal immune system must maintain a delicate balance between immune tolerance to commensals and protective immune responses to pathogens. There is growing evidence that gut microbiota is required for the generation of the appropriate gut immune system. However, little is known about the role of individual bacterial species. We addressed this issue using gnotobiotic mice, in which only certain known strains of bacteria are present. Gut microbiota is crucial for the development of Th17 cells, because germ-free (GF) mice lack Th17 cells in the small intestinal lamina propria. To identify the bacterial species that induce Th17 cells, we generated gnotobiotic mice by colonizing GF mice with several sets of bacterial species indigenous to mice. One bacterial species, segmented filamentous bacteria (SFB), specifically induced the accumulation of Th17 cells in the small intestine. Furthermore, SFB colonization enhanced resistance to the intestinal pathogen Citrobacter rodentium. Regulatory T (Treg) cells are essential for maintaining immune tolerance and immune homeostasis. Treg cells are present in higher densities in the intestine, particularly in the colon, than in other organs. Treg cells are induced by gut microbiota because of a significant decrease in the colon of GF mice. We observed a marked increase in colonic Treg numbers after colonization of GF mice with a mixture of 46 Clostridium strains isolated from the feces of conventional mice. To extend the clinical relevance, we tried to identify Treg-inducing bacterial strains derived from human feces. Similar to bacteria indigenous to mice, 17 strains of Treg-inducing bacteria belonging to Clostridiales displayed a potent capacity to induce colonic Treg cells. Finally, we assessed the potential benefits of Treg-inducing bacterial strains. The mice treated with the 17 strains were resistant to TNBS-induced colitis and OVA-induced allergic diarrhea.
