Interferons (IFNs) have a central role in immunity. They trigger intrinsic immune responses to infections by activating protective transcriptional programmes, and they also prompt innate and adaptive immune responses. IFN production is tightly regulated; excess IFN can cause overactivation of the immune system, potentially leading to events such as the ‘cytokine storm’.

In a true immunological tour de force, a preprint by Ngo et al. (not peer reviewed) addresses the important role of plasmacytoid dendritic cells (pDCs), as the main producers of type I IFN (IFN-I), in the pathology of various viral infections. pDCs sense viral RNA and DNA through Toll-like receptor 7 (TLR7) and TLR9, respectively, which leads to IFN-I production and antiviral immunity. Thus, the role of pDCs in infection has long been thought to be protective; however, the most precise mouse model for transient depletion of pDCs — injection of diphtheria toxin into BDCA2-hDTR-transgenic mice — triggers IFN-I responses that can confound results. Here, Ngo et al. developed a model to deplete pDCs constitutively on the basis of their unique co-expression of the genes Siglech and Pacsin1, which effectively ablates pDCs without major effects on other cell lineages.