Mehrdad Matloubian, MD, PhD
The main research interest of our laboratory is to gain a detailed understanding of pathways involved in the initiation and resolution of innate immune responses to a pathogen and how they shape the subsequent adaptive immune response. Our current focus is on type I interferons, IFN-α/β, since they are the major components of the initial response to a viral infection and play a crucial role in both inhibiting viral replication and promoting T and B cell responses. Since prolonged IFN production can be detrimental to the organism, the IFN response is tightly regulated. Shortly after viral infection there is a tremendous but transient increase in IFN levels with a rapid return to homeostatic levels despite ongoing viral replication, which is the initial trigger for IFN production. The negative regulatory pathways that inhibit continued IFN production in the presence of active viral replication are not completely understood. Using a mouse model of viral infection with lymphocytic choriomeningitis virus we have identified the viral sensing pathways that initiate IFN production in vivo. We have found that activation of two distinct pathways in two different cell types contributes to IFN production. Our current work focuses on identifying factors that negatively regulate each pathway. We hope that insights gained from these basic studies will be applicable to understanding and treating diseases, such as lupus, where IFNs have been established to contribute significantly to their pathogenesis.