Since ISG15 is a ubiquitin-like modifier that is known to be covalently linked to hundreds of cellular and several viral substrates (Giannakopoulos et al., 2005; Zhao et al., 2005), our goal was to identify which substrates following overexpression of ISG15 could account for the protective effect detected in the context of Listeria infection and used a proteomic approach. Here, ISG15 is linked to listeriosis.