Length does matter for cGAS

Recognition of foreign nucleic acids by the immune system is essential to host protection against many viral and bacterial infections. It relies on the capacity of innate immune sensors to selectively distinguish self‐ and non‐self‐nucleic acids, on the basis of a variety of parameters including base modifications, sequence composition, length or subcellular localisation. In this issue of EMBO Reports, Luecke et al 1 describe that the sensing of cytoplasmic double‐stranded DNA by the cyclic GMP–AMP (cGAMP) synthase (cGAS) is much more sensitive for longer fragments, when low doses of cytoplasmic DNA are used. This finding repositions length as the predominant factor governing the discrimination between self‐ and non‐self‐cytoplasmic DNA.