Adaptive immunity in the host-microbiota dialog

Abstract

The intestinal tract represents the largest mucosal surface and is a major site of multifaceted interactions between the host mucosal immune system and components of the intestinal microbiota. Host immune responses to the commensal microbiota are tightly controlled and, meanwhile, the microbiota actively shapes intestinal immune responses to itself. Appreciation of these interactions during health and disease may direct therapeutic approaches to a broad range of autoimmune and inflammatory disorders in humans. In this review, we will discuss findings on how the intestinal immune system, especially adaptive immune cells, helps accommodate the large number of resident bacteria, and in turn how the microbiota shapes intestinal immune responses to achieve mutualism.

Figure 1. Treg-IgA-microbiota as a functional unit

Treg cells are the major helper cells for microbiota antigen-specific IgA responses. This finding leads to the concept that the overall purpose of IgA and Treg cells in the intestine is to maintain mutualism with the microbiota and restrict intestinal inflammation. Intestinal inflammation reduces anaerobic microbiota such as the Firmicutes, and allows oxygen-tolerant organisms and pathogens such as the Proteobacteria to bloom^, . The microbiota is well adapted to compete with pathogens for luminal nutrients, minimizing colonization of the pathogens. Treg cells, IgA, and the microbiota act together as a functional triad to protect the host from pathogens, which is likely to be more effective than IgA would be alone.

Figure 2. “Two-hit model” of microbiota for the pathogenesis of colitis

Once intestinal immune homeostasis breaks, the microbiota stimulates mucosal DCs to produce IL-6 via TLR ligation. IL-6 promotes spontaneous proliferation of naïve T cells, which are in T0 status. T0 cells, in response to microbial antigens in the lamina propria, proliferate and upon TCR stimulation differentiate into Th1 and Th17 cells under the influence of IL-12 and IL-6/TGF-β, respectively, which eventually leads to intestinal inflammation. Adapted from Feng et al J Exp Med, 207, 1321–1332 (2010).