We are interested in cell death and inflammatory responses as two critical components of the host immune defense against pathogens. We use forward genetic analysis in the wild-derived strains of mice to investigate regulatory mechanisms of cell death and inflammation. Our recent work has uncovered importance of constitutive (tonic) type I Interferon (IFN-I) in initiation of programed cell death such as pyroptosis and necroptosis. This constitutive IFN signature is induced by STING-mediated DNA-sensing pathway and maintains the expression of unknown effectors of necroptosis. We are currently focusing on identifying these effectors by means of forward genetic analysis.