title: ISG15 counteracts Listeria monocytogenes infection.
abstract: 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.
authors.affiliation: Unité, Institut Pasteur, Paris, France.
authors.forename: Lilliana
authors.initials: L
authors.lastname: Radoshevich
authors.affiliation: Unité, Institut Pasteur, Paris, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Impens
authors.affiliation: Unité, Institut Pasteur, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Ribet
authors.affiliation: Unité, Institut Pasteur, Paris, France.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Quereda
authors.affiliation: Unité, Institut Pasteur, Paris, France.
authors.forename: To
authors.initials: T
authors.lastname: Nam Tham
authors.affiliation: Unité, Institut Pasteur, Paris, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nahori
authors.affiliation: Institut National de la Recherche Agronomique, UMR1319, Micalis, AgroParisTech, Jouy-en-Josas, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bierne
authors.affiliation: Unité, Institut Pasteur, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dussurget
authors.affiliation: Unité, Institut Pasteur, Paris, France.
authors.forename: Javier
authors.initials: J
authors.lastname: Pizarro-Cerdá
authors.affiliation: Molecular Genetics Group, Neuropathologie, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Knobeloch
authors.affiliation: Unité, Institut Pasteur, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000737:chemistry; D020869:Gene Expression Profiling; D006056:Golgi Apparatus / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D007553:Isotope Labeling; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008810:Mice, Inbred C57BL; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D014452:Ubiquitins; C074034:ISG15 protein, human
keywords: ISG15; ISGylation; Listeria monocytogenes; cell biology; endoplasmic reticulum; human; infectious disease; innate immunity; microbiology; mouse