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Optineurin deficiency in mice is associated with increased sensitivity to Salmonella but does not affect proinflammatory NF-κB signaling

Karolina Slowicka (UGent) , Lars Vereecke (UGent) , Conor Mc Guire (UGent) , Mozes Sze (UGent) , Jonathan Maelfait (UGent) , Annasaheb Kolpe (UGent) , Xavier Saelens (UGent) , Rudi Beyaert (UGent) and Geert van Loo (UGent)
(2016) EUROPEAN JOURNAL OF IMMUNOLOGY. 46(4). p.971-980
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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-kappa B 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-kappa B activation could be observed in OPTN knockoutmice or fibroblasts derived from thesemice 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.
Keywords
Inflammation, Autophagy, Innate immunity, Interferon, NF-kappa B, Optineurin, AMYOTROPHIC-LATERAL-SCLEROSIS, AUTOPHAGY RECEPTOR OPTINEURIN, OPEN-ANGLE GLAUCOMA, SELECTIVE AUTOPHAGY, ACTIVATION, BINDING, GENE, PHOSPHORYLATION, DISRUPTION, EXPRESSION

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Citation

Please use this url to cite or link to this publication:

Chicago
Slowicka, Karolina, Lars Vereecke, Conor Mc Guire, Mozes Sze, Jonathan Maelfait, Annasaheb Kolpe, Xavier Saelens, Rudi Beyaert, and Geert van Loo. 2016. “Optineurin Deficiency in Mice Is Associated with Increased Sensitivity to Salmonella but Does Not Affect Proinflammatory NF-κB Signaling.” European Journal of Immunology 46 (4): 971–980.
APA
Slowicka, K., Vereecke, L., Mc Guire, C., Sze, M., Maelfait, J., Kolpe, A., Saelens, X., et al. (2016). Optineurin deficiency in mice is associated with increased sensitivity to Salmonella but does not affect proinflammatory NF-κB signaling. EUROPEAN JOURNAL OF IMMUNOLOGY, 46(4), 971–980.
Vancouver
1.
Slowicka K, Vereecke L, Mc Guire C, Sze M, Maelfait J, Kolpe A, et al. Optineurin deficiency in mice is associated with increased sensitivity to Salmonella but does not affect proinflammatory NF-κB signaling. EUROPEAN JOURNAL OF IMMUNOLOGY. 2016;46(4):971–80.
MLA
Slowicka, Karolina, Lars Vereecke, Conor Mc Guire, et al. “Optineurin Deficiency in Mice Is Associated with Increased Sensitivity to Salmonella but Does Not Affect Proinflammatory NF-κB Signaling.” EUROPEAN JOURNAL OF IMMUNOLOGY 46.4 (2016): 971–980. Print.
@article{7176875,
  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-kappa B 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-kappa B activation could be observed in OPTN knockoutmice or fibroblasts derived from thesemice 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.},
  author       = {Slowicka, Karolina and Vereecke, Lars and Mc Guire, Conor and Sze, Mozes and Maelfait, Jonathan and Kolpe, Annasaheb and Saelens, Xavier and Beyaert, Rudi and van Loo, Geert},
  issn         = {0014-2980},
  journal      = {EUROPEAN JOURNAL OF IMMUNOLOGY},
  keyword      = {Inflammation,Autophagy,Innate immunity,Interferon,NF-kappa B,Optineurin,AMYOTROPHIC-LATERAL-SCLEROSIS,AUTOPHAGY RECEPTOR OPTINEURIN,OPEN-ANGLE GLAUCOMA,SELECTIVE AUTOPHAGY,ACTIVATION,BINDING,GENE,PHOSPHORYLATION,DISRUPTION,EXPRESSION},
  language     = {eng},
  number       = {4},
  pages        = {971--980},
  title        = {Optineurin deficiency in mice is associated with increased sensitivity to Salmonella but does not affect proinflammatory NF-\ensuremath{\kappa}B signaling},
  url          = {http://dx.doi.org/10.1002/eji.201545863},
  volume       = {46},
  year         = {2016},
}

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