Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice

Tenascin C (TNC) is an extracellular matrix glycoprotein that recently emerged as an immunomodulator. TNC-deficient (TNC−/−) mice were reported to have a reduced inflammatory response upon systemic administration of lipopolysaccharide, the toxic component of gram-negative bacteria. Here, we investig...

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Main Authors: Mariska T. Meijer, Alex F. de Vos, Brendon P. Scicluna, Joris J. Roelofs, Chérine Abou Fayçal, Gertraud Orend, Fabrice Uhel, Tom van der Poll
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.600979/full
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author Mariska T. Meijer
Mariska T. Meijer
Alex F. de Vos
Alex F. de Vos
Brendon P. Scicluna
Brendon P. Scicluna
Brendon P. Scicluna
Joris J. Roelofs
Chérine Abou Fayçal
Gertraud Orend
Fabrice Uhel
Fabrice Uhel
Tom van der Poll
Tom van der Poll
Tom van der Poll
spellingShingle Mariska T. Meijer
Mariska T. Meijer
Alex F. de Vos
Alex F. de Vos
Brendon P. Scicluna
Brendon P. Scicluna
Brendon P. Scicluna
Joris J. Roelofs
Chérine Abou Fayçal
Gertraud Orend
Fabrice Uhel
Fabrice Uhel
Tom van der Poll
Tom van der Poll
Tom van der Poll
Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice
Frontiers in Immunology
tenascin C
sepsis
Klebsiella pneumoniae (K. pneumoniae)
pneumonia
alarmins
innate immunity
author_facet Mariska T. Meijer
Mariska T. Meijer
Alex F. de Vos
Alex F. de Vos
Brendon P. Scicluna
Brendon P. Scicluna
Brendon P. Scicluna
Joris J. Roelofs
Chérine Abou Fayçal
Gertraud Orend
Fabrice Uhel
Fabrice Uhel
Tom van der Poll
Tom van der Poll
Tom van der Poll
author_sort Mariska T. Meijer
title Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice
title_short Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice
title_full Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice
title_fullStr Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice
title_full_unstemmed Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice
title_sort tenascin-c deficiency is associated with reduced bacterial outgrowth during klebsiella pneumoniae-evoked pneumosepsis in mice
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2021-03-01
description Tenascin C (TNC) is an extracellular matrix glycoprotein that recently emerged as an immunomodulator. TNC-deficient (TNC−/−) mice were reported to have a reduced inflammatory response upon systemic administration of lipopolysaccharide, the toxic component of gram-negative bacteria. Here, we investigated the role of TNC during gram-negative pneumonia derived sepsis. TNC+/+ and TNC−/− mice were infected with Klebsiella pneumoniae via the airways and sacrificed 24 and 42 h thereafter for further analysis. Pulmonary TNC protein levels were elevated 42 h after infection in TNC+/+ mice and remained undetectable in TNC−/− mice. TNC−/− mice showed modestly lower bacterial loads in lungs and blood, and a somewhat reduced local—but not systemic—inflammatory response. Moreover, TNC−/− and TNC+/+ mice did not differ with regard to neutrophil recruitment, lung pathology or plasma markers of distal organ injury. These results suggest that while TNC shapes the immune response during lipopolysaccharide-induced inflammation, this role may be superseded during pneumosepsis caused by a common gram-negative pathogen.
topic tenascin C
sepsis
Klebsiella pneumoniae (K. pneumoniae)
pneumonia
alarmins
innate immunity
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.600979/full
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spelling doaj-3ff9ccd3d5ee4cfba65396a6d24c84a22021-03-11T05:05:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.600979600979Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in MiceMariska T. Meijer0Mariska T. Meijer1Alex F. de Vos2Alex F. de Vos3Brendon P. Scicluna4Brendon P. Scicluna5Brendon P. Scicluna6Joris J. Roelofs7Chérine Abou Fayçal8Gertraud Orend9Fabrice Uhel10Fabrice Uhel11Tom van der Poll12Tom van der Poll13Tom van der Poll14Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, NetherlandsClinical Epidemiology Biostatistics and Bioinformatics, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Pathology, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsThe Tumor Microenvironment Laboratory, INSERM UMR_S 1109, Université Strasbourg, Faculté de Médecine, Hopital Civil, Institut d'Hématologie et d'Immunologie, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, FranceThe Tumor Microenvironment Laboratory, INSERM UMR_S 1109, Université Strasbourg, Faculté de Médecine, Hopital Civil, Institut d'Hématologie et d'Immunologie, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, FranceCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, NetherlandsDivision of Infectious Diseases, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsTenascin C (TNC) is an extracellular matrix glycoprotein that recently emerged as an immunomodulator. TNC-deficient (TNC−/−) mice were reported to have a reduced inflammatory response upon systemic administration of lipopolysaccharide, the toxic component of gram-negative bacteria. Here, we investigated the role of TNC during gram-negative pneumonia derived sepsis. TNC+/+ and TNC−/− mice were infected with Klebsiella pneumoniae via the airways and sacrificed 24 and 42 h thereafter for further analysis. Pulmonary TNC protein levels were elevated 42 h after infection in TNC+/+ mice and remained undetectable in TNC−/− mice. TNC−/− mice showed modestly lower bacterial loads in lungs and blood, and a somewhat reduced local—but not systemic—inflammatory response. Moreover, TNC−/− and TNC+/+ mice did not differ with regard to neutrophil recruitment, lung pathology or plasma markers of distal organ injury. These results suggest that while TNC shapes the immune response during lipopolysaccharide-induced inflammation, this role may be superseded during pneumosepsis caused by a common gram-negative pathogen.https://www.frontiersin.org/articles/10.3389/fimmu.2021.600979/fulltenascin CsepsisKlebsiella pneumoniae (K. pneumoniae)pneumoniaalarminsinnate immunity