Interferons are a family of cytokines with antiviral and immunomodulatory properties. There are three families of interferons and hundreds of interferon stimulated genes. We study type I and type III interferons, which induce an overlapping set of genes in different cell types, and their mechanisms of action in the intestine.
The role of interferon in enteric immunity
We have found that type I and type III interferon have complementary roles in control of persistent murine norovirus infection in the intestine. Type I interferon prevents spread of viral infection to systemic organs whereas type III interferon controls viral replication within the intestine. Treatment of mice with recombinant type III interferon (also known as Interferon Lambda or IL-28) prevents infection and clears an established persistent infection. This clearance of persistent norovirus infection does not require the action of adaptive immunity, indicating that an innate immune response is sufficient for clearance of this persistent infection. Future work will define the cells and interferon stimulated genes that execute this innate antiviral response in the intestine.
Tonic interferon signaling in intestinal health and disease
The intestine is home to billions of bacteria. Intestinal bacteria are sensed by intestinal immune cells and alter the immune response to infection and susceptibility to disease. Sensing of microbial products in some settings is known to induce expression of interferon. Indeed, we have detected low-level expression of interferon-stimulated genes in the intestine, but the consequences of this tonic interferon signaling are not completely understood. We are interested in further studying the physiological effects of this tonic interferon signaling on immunity to infection and susceptibility to disease.