title: The Salmonella Effector Protein SopA Modulates Innate Immune Responses by Targeting TRIM E3 Ligase Family Members.
abstract: Salmonella Typhimurium stimulates inflammatory responses in the intestinal epithelium, which are essential for its ability to replicate within the intestinal tract. Stimulation of these responses is strictly dependent on the activity of a type III secretion system encoded within its pathogenicity island 1, which through the delivery of effector proteins, triggers signaling pathways leading to inflammation. One of these effectors is SopA, a HECT-type E3 ligase, which is required for the efficient stimulation of inflammation in an animal model of Salmonella Typhimurium infection. We show here that SopA contributes to the stimulation of innate immune responses by targeting two host E3 ubiquitin ligases, TRIM56 and TRIM65. We also found that TRIM65 interacts with the innate immune receptor MDA5 enhancing its ability to stimulate interferon-β signaling. Therefore, by targeting TRIM56 and TRIM65, SopA can stimulate signaling through two innate immune receptors, RIG-I and MDA5. These findings describe a Salmonella mechanism to modulate inflammatory responses by directly targeting innate immune signaling mechanisms.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Jana
authors.initials: J
authors.lastname: Kamanova
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Lara-Tejero
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Galán
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D002460:Cell Line; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D006790:Host-Parasite Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D044767:Ubiquitin-Protein Ligases; C060971:SopA protein, Bacteria