ISG15 and viral infectious disease: Increased cytokine secretion mediated by ISG15 is a previously uncharacterized way for the host to engage the immune system to combat both bacterial and viral infection; the first cells that encounter Listeria, (i.e., nonphagocytic cells) which are able to induce ISG15 at early time points could raise the alarm against an invading pathogen and as a result help alert innate immune cells to the site of infection.