Engagement of programmed cell death by nucleic acid sensing

Abstract

During infection, the sensing of foreign nucleic acids inside an infected cell is often the first line of immunological defense. When DNA or RNA is sensed, one outcome is the production of anti-viral signaling molecules such as type I interferons. Additionally, cells can undergo programmed cell death. Here we describe the mechanism of induction of the programmed cell death pathway, necroptosis, following detection of cytosolic DNA or RNA. Necroptosis is a lytic and proinflammatory form of cell death, that can eliminate infected cells and alert and instruct the immune system. We show that following sensing of foreign nucleic acids, induction of necroptosis relies on the production of both anti-viral interferon, as well pro-inflammatory molecule, tumor necrosis factor.