A role for IL-22 in the relationship between intestinal helminths, gut microbiota and mucosal immunity

Abstract

The intestinal tract is home to nematodes as well as commensal bacteria (microbiota), which have coevolved with the mammalian host. The mucosal immune system must balance between an appropriate response to dangerous pathogens and an inappropriate response to commensal microbiota that may breach the epithelial barrier, in order to maintain intestinal homeostasis. IL-22 has been shown to play a critical role in maintaining barrier homeostasis against intestinal pathogens and commensal bacteria. Here we review the advances in our understanding of the role of IL-22 in helminth infections, as well as in response to commensal and pathogenic bacteria of the intestinal tract. We then consider the relationship between intestinal helminths and gut microbiota and hypothesize that this relationship may explain how helminths may improve symptoms of inflammatory bowel diseases. We propose that by inducing an immune response that includes IL-22, intestinal helminths may enhance the mucosal barrier function of the intestinal epithelium. This may restore the mucosal microbiota populations from dysbiosis associated with colitis and improve intestinal homeostasis.

Fig. 1

A model for gastrointestinal helminth infection stimulating the production of IL-22 by innate lymphoid cells (ILCs) and T_H22 cells, in combination with the T_H2 cytokines, IL-4 and IL-13, which will stimulate the increased turnover and proliferation of intestinal epithelial cells as well as mucus production by goblet cells. This will reduce the attachment of bacteria to the epithelial cells, especially from the phylum Proteobacteria, and restore the microbial community diversity that was reduced as a result of dysbiosis during intestinal inflammation.