ISG15 counteracts Listeria monocytogenes infection

• DOI: 10.7554/elife.06848
• Publication Date: 2015-08-10T14:15:54Z
• Authors: Lilliana Radoshevich; Francis Impens; David Ribet; Juan J Quereda; To Nam Tham; Marie-Anne Nahori; Hélène Bierne; Olivier Dussurget; Javier Pizarro-Cerdá; Klaus-Peter Knobe...; Pascale Cossart
• Keywords: 0301 basic medicine; 570; ISG15; QH301-705.5; Science; 610; Golgi Apparatus; Infectious Disease; [SDV.BC]Life Sciences [q-bio]/Cellular Biology; souris; Endoplasmic Reticulum; 03 medical and health sciences; Animals; Humans; maladie infectieuse; Listeriosis; réticulum endoplasmique; microbiologie; Biology (General); innate immunity; Ubiquitins; Gene Expression Profiling; Q; R; Cell Biology; Listeria monocytogenes; Innate Immunity; Immunity, Innate; 3. Good health; Mice, Inbred C57BL; endoplasmic reticulum; [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology; ISGylation; Isotope Labeling; Medicine; Cytokines; listeria monocytogènes; immunité; Endoplasmic reticulum; HeLa Cells

ISG15 is an interferon-stimulated, linear di-ubiquitin-like protein, with anti-viral activity. The role of ISG15 during bacterial infection remains elusive. We show that ISG15 expression in nonphagocytic cells is dramatically induced upon Listeria infection. Surprisingly this induction can be type I interferon independent and depends on the cytosolic surveillance pathway, which senses bacterial DNA and signals through STING, TBK1, IRF3 and IRF7. Most importantly, we observed that ISG15 expression restricts Listeria infection in vitro and in vivo. We made use of stable isotope labeling in tissue culture (SILAC) to identify ISGylated proteins that could be responsible for the protective effect. Strikingly, infection or overexpression of ISG15 leads to ISGylation of ER and Golgi proteins, which correlates with increased secretion of cytokines known to counteract infection. Together, our data reveal a previously uncharacterized ISG15-dependent restriction of Listeria infection, reinforcing the view that ISG15 is a key component of the innate immune response.