Differential signaling by type-I and type-III interferons in mucosa

Mucosal surfaces are barrier sites that protect the body from the outside environment. They have developed mechanisms to responsive to pathogens. Cells at mucosal surfaces rely on both the type-I and -III interferons (IFNs) as key cytokines to protect the epithelium itself and to prevent systemic spread of viral infections. Type-I and -III IFNs have been shown to use distinct receptors but similar JAK/STAT signaling cascades to elicit the induction of IFN-stimulated genes. These overlapping cascades led to the original hypothesis that both IFNs provided redundant functions at mucosal surfaces. However, accumulating evidence points toward a different model where each IFN provides a unique protective and homeostatic function as well as distinct antiviral protection to epithelial cells. This review will highlight recent work shedding light on the differences in how both type -I and -III IFNs induce receptormediated signaling to protect mucosal surfaces.