Pathogen Resistance Mediated by IL-22 Signaling at the Epithelial-Microbiota Interface.
Intestinal colonization resistance to bacterial pathogens is generally associated, among other factors, with mucosal homeostasis that preserves the integrity of the intestinal barrier. Mucosal homeostasis depends on physical and molecular interactions between three components: the resident microbiota, the epithelial layer and the local immune system. The cytokine IL-22 helps to orchestrate this three-way interaction. IL-22 is produced by immune cells present beneath the epithelium and is induced by bacteria present in the intestine. IL-22 stimulates the epithelial cells via the IL-22RA1-IL-10R2 receptor complex inducing changes in the expression of genes involved in the maintenance of epithelial barrier integrity, with a variety of functions in pathogen resistance such as mucus layer modifications and hydration, tight junction fortification and the production of a broad range of bactericidal compounds. These mechanisms of pathogen resistance, in turn, affect the microbiota composition and create an environment that excludes pathogens. Here we highlight the role of IL-22 as key mediator in the give-and-take relationship between the microbiota and the host that impacts pathogen resistance.
Host-Microbiota Interactions Laboratory, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom. Electronic address: fs1@sanger.ac.uk.
Fernanda
F
Schreiber
Host-Microbiota Interactions Laboratory, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom. Electronic address: ma9@sanger.ac.uk.
Julia Maryam
JM
Arasteh
Host-Microbiota Interactions Laboratory, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom. Electronic address: tl2@sanger.ac.uk.
Trevor D
TD
Lawley
D001424:Bacterial Infections / Q000378:metabolism / Q000382:microbiology; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D018123:Receptors, Interleukin / Q000378:metabolism*; D015398:Signal Transduction
C433253:IL22RA2 protein, human; D018123:Receptors, Interleukin
IL-22 signaling; epithelium; intestinal microbiota; mucus; pathogen resistance