Abstract

A central function of our innate immune system is to sense microbial pathogens by the presence of their nucleic acid genomes or their transcriptional or replicative activity. In mammals, a receptor-based system is mainly responsible for the detection of these “non‐ self” nucleic acids. Tremendous progress has been made in the past years to identify host constituents that are required for this intricate task. With regard to the sensing of RNA genome based pathogens by our innate immune system, a picture is emerging that includes certain families of the toll-like receptor family (TLR3, TLR7 , TLR8) and the RIG - I like helicases (RIG-I, MDA5 and LGP2 ). Genetic loss of function studies implicate that the absence of these pathways can lead to a complete lack of recognition of certain RNA viruses. At the same time, intracellular DNA can also trigger potent innate immune responses, yet the players in this field are less clear. We and another group recently identified a role for RNA polymerase III in the conversion of AT-rich DNA into an RNA ligand that is sensed by the RIG ‐I pathway.