Although ISG15 and ISGylation have been primarily characterized in the context of viral infection, it was recently shown that ISG15 also protects against infections by intracellular bacteria such as Listeria monocytogenes (L. monocytogenes) and Mycobacterium tuberculosis (M. tuberculosis) or predominantly extracellular bacteria like Pseudomonas aeruginosa (38–40). This evidence concerns the gene ISG15 and infection.