Regulation of host/pathogen interactions in the gastrointestinal tract by type I and III interferons

Abstract

Interferons (IFNs) are an integral component of the host innate immune response during viral infection. Recent advances in the study of type I and III IFNs suggest that though both types counteract viral infection, type III IFNs act predominantly at epithelial barrier sites, while type I IFNs drive systemic responses. The dynamics and specific roles of type I versus III IFNs have been studied in the context of infection by a variety of enteric pathogens, including reovirus, rotavirus, norovirus, astrovirus, and intestinal severe acute respiratory syndrome coronavirus 2, revealing shared patterns of regulatory influence. An important role for the gut microbiota, including the virome, in regulating homeostasis and priming of intestinal IFN responses has also recently emerged.

Fig. 1.

Reovirus, rotavirus, and SARS-CoV-2 infect enterocytes. Astrovirus displays tropism for enterocytes and goblet cells, and norovirus infects tuft cells. Upon infection, type III interferon (IFN) is induced and acts upon the intestinal epithelium to prevent viral infection and replication within the intestinal epithelium, whereas type I IFN, which is produced by epithelial and immune cells, acts to limit systemic spread of enteric viruses. In the uninfected intestine, commensal microbes and the virome induce steady-state, tonic expression of type I and type III IFN in immune cells and epithelial cells respectively.