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

Mariska T Meijer,Gertraud Orend,Brendon P Scicluna,Joris J Roelofs,Alex F De Vos,Fabrice Uhel,Tom Van Der Poll,Chérine Abou Fayçal

doi:10.3389/fimmu.2021.600979

Abstract

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suggest that while TNC shapes the immune response during lipopolysaccharide-induced inflammation, this role may be superseded during pneumosepsis caused by a common gram-negative pathogen.

Highlights

Tenascin C (TNC) is a large multimeric extracellular matrix glycoprotein with binding sites for many different signaling factors
Infection with K. pneumoniae via the airways resulted in a gradual rise in lung TNC levels that at 42 h was more than 10-fold over those measured in naïve mice [42 h: 110.8 (46.5-264.1) ng/mL, p < 0.01]
We investigated the hypothesis that TNC may play a role in the enhancement of inflammatory responses during sepsis

Summary

Introduction

Tenascin C (TNC) is a large multimeric extracellular matrix glycoprotein with binding sites for many different signaling factors. It plays a major role during embryonic development, but in adult tissues expression levels are relatively low [1, 2]. TNC−/− mice became less severely ill after LPS injection, which was associated with decreased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production [7]. Together these data suggest that TNC may enhance acute and chronic inflammation

Methods

Results

Conclusion