title: Optineurin deficiency in mice is associated with increased sensitivity to Salmonella but does not affect proinflammatory NF-κB signaling.
abstract: Optineurin (OPTN) is an evolutionary conserved and ubiquitously expressed ubiquitin-binding protein that has been implicated in glaucoma, Paget bone disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases. From in vitro studies, OPTN was shown to suppress TNF-induced NF-κB signaling and virus-induced IRF signaling, and was identified as an autophagy receptor required for the clearance of cytosolic Salmonella upon infection. To assess the in vivo functions of OPTN in inflammation and infection, we generated OPTN-deficient mice. OPTN knockout mice are born with normal Mendelian distribution and develop normally without any signs of spontaneous organ abnormality or inflammation. However, no differences in NF-κB activation could be observed in OPTN knockout mice or fibroblasts derived from these mice upon TNF or LPS treatment. Primary bone marrow-derived macrophages from OPTN-deficient mice had slightly impaired IRF signaling and reduced IFN type I production in response to LPS or poly(I,C). Finally, OPTN-deficient mice were more susceptible to infection with Salmonella, confirming in vivo the importance of OPTN in bacterial clearance.
authors.affiliation: Inflammation Research Center, Unit of Cellular and Molecular (Patho)physiology, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Karolina
authors.initials: K
authors.lastname: Slowicka
authors.affiliation: Inflammation Research Center, Unit of Cellular and Molecular (Patho)physiology, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Lars
authors.initials: L
authors.lastname: Vereecke
authors.affiliation: Inflammation Research Center, Unit of Cellular and Molecular (Patho)physiology, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Conor
authors.initials: C
authors.lastname: Mc Guire
authors.affiliation: Inflammation Research Center, Unit of Cellular and Molecular (Patho)physiology, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Mozes
authors.initials: M
authors.lastname: Sze
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Maelfait
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.|Medical Biotechnology Centre, Ghent, Belgium.
authors.forename: Annasaheb
authors.initials: A
authors.lastname: Kolpe
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.|Medical Biotechnology Centre, Ghent, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.|Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, Ghent, Belgium.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
authors.affiliation: Inflammation Research Center, Unit of Cellular and Molecular (Patho)physiology, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: van Loo
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D005136:Eye Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007370:Interferon Type I / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D011070:Poly I-C / Q000494:pharmacology; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D018797:Cell Cycle Proteins; D005136:Eye Proteins; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; C494233:Irf3 protein, mouse; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D016328:NF-kappa B; C501288:Optn protein, mouse; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C
keywords: Autophagy ⋅ Inflammation ⋅ Innate immunity ⋅ Interferon ⋅ NF-κB ⋅ Optineurin