Frontiers in Immunology (Mar 2021)

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

  • 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

DOI
https://doi.org/10.3389/fimmu.2021.600979
Journal volume & issue
Vol. 12

Abstract

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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suggest that while TNC shapes the immune response during lipopolysaccharide-induced inflammation, this role may be superseded during pneumosepsis caused by a common gram-negative pathogen.

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