ISG15 and infection: While we did not detect increased levels of Ifna1 and Ifnab1 upon infection either in the complete caecum or IECs (Supplementary Figs. 13 and 14), the expanded Isg15-expressing enterocyte population co-expressed Ddx60 and Irf7. Upon cytosolic-sensing of self- and non-self nucleic acids, DDX60 promotes retinoic-acid inducible gene I (RIG-I)-like receptor-mediated signalling that results in Isg15 expression via the IFN regulatory factors 3 and 7 (IRF3, IRF7)22,55.