Optineurin deficiency in mice is associated with increased sensitivity to Salmonella but does not affect proinflammatory NF‐κB signaling |
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Authors: | Karolina Slowicka Lars Vereecke Conor Mc Guire Mozes Sze Jonathan Maelfait Annasaheb Kolpe Xavier Saelens Rudi Beyaert Geert van Loo |
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Affiliation: | 1. Inflammation Research Center, Unit of Cellular and Molecular (Patho)physiology, Ghent, Belgium;2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium;3. Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK;4. Medical Biotechnology Centre, Ghent, Belgium;5. Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, Ghent, Belgium |
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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. |
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Keywords: | Autophagy ⋅ Inflammation ⋅ Innate immunity ⋅ Interferon ⋅ NF‐κ B ⋅ Optineurin |
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