Type I and III Interferon in the Gut: Tight Balance between Host Protection and Immunopathology

Johanna Pott, Silvia Stockinger

The intestinal mucosa forms an active interface to the outside word, facilitating nutrient and water uptake and at the same time acts as a barrier toward the highly colonized intestinal lumen. A tight balance of the mucosal immune system is essential to tolerate harmless antigens derived from food or commensals and to effectively defend against potentially dangerous pathogens. Interferons (IFN) provide a first line of host defense when cells detect an invading organism. Whereas type I IFN were discovered almost 60 years ago, type III IFN were only identified in the early 2000s. It was initially thought that type I IFN and type III IFN performed largely redundant functions. However, it is becoming increasingly clear that type III IFN exert distinct and non-redundant functions compared to type I IFN, especially in mucosal tissues. Here, we review recent progress made in unraveling the role of type I/III IFN in intestinal mucosal tissue in the steady state, in response to mucosal pathogens and during inflammation.