The commensal microbiota drives immune homeostasis

Abstract

For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.

Keywords: immune homeostasis; intestinal microbiota.

Figure 1

The microbiota helps to maintain immune homeostasis by stimulating different arms of the T cell response. (A) SFB is a potent inducer of Th17 cells, whereas pathogens like S. typhimurium induce an effector Th1 response. PSA from B. fragilis stimulates the differentiation of FoxP3+ T cells, which downregulate the pro-inflammatory Th1 and Th17 responses. (B) Different environmental and host-derived factors are known to cause dysbiosis. Imbalances in the intestinal microbiota can favor Th17 pro-inflammatory T cells over regulatory FoxP3+ T cells, inducing inflammatory response that can damage the intestinal epithelium. In a genetically predisposed host this can lead to chronic inflammatory disease, such as IBD or autoimmunity.