To test whether ISG15 and ISGylation are induced upon bacterial infection, we infected HeLa cells with Listeria. Upon L. monocytogenes infection, ISG15 was massively induced, whereas incubation with the related non-pathogenic bacterium, Listeria innocua, did not lead to an increase in ISG15 production (Figure 1A). Here, ISG15 is linked to bacterial infectious disease.