Our research focuses on studying the complex, dynamic interplay that occursbetween two distinct biological systems, the prokaryotic pathogen and theeukaryotic host. We have shown that 2 important innate immune pathways, type IIFN and the inflammasome, are sequentially linked during bacterial infections ofmacrophages. This 2-tiered innate immune response serves as a way for thehost to gauge the level of “danger” before commitment to critical host responsessuch as cell death. For example, we have shown that dsDNA from cytosolicbacteria, such as Francisella, elicits type I IFN responses within two hours ofinfection. If the bacteria are capable of replicating, increased levels of dsDNAtrigger an AIM2 inflammasome and proinflammatory cell death, which eliminatesthe intracellular niche and is a host defense mechanism. Importantly, we haveshown a similar dependency on type I IFN during Salmonella infections thatactivates caspase-11 in non-canonical inflammasomes and triggers host celldeath. Thus, a comparative analysis of the molecular pathways necessary forrecognition of two facultative intracellular pathogens, Francisella and Salmonella,has highlighted the role of type I IFN in potentiating cell death pathways.