(403) Epithelial tissue factor drives pneumococcus-mediated necrosuppurative pneumonia

Introduction/Rationale: Pulmonary infections induce heterogeneous lung immune responses, resulting in multiple pneumonia histopathology sub-phenotypes. Necrosuppurative pneumonia is characterized by alveolar necrosis, neutrophils, edema, and airspace fibrin accumulation, observed in human autopsies and S. pneumoniae (Sp)-infected mice. We endeavor to elucidate innate immunity mechanisms leading to the necrosuppurative sub-phenotype of pneumonia.

Methods: We compared outcomes of Sp pneumonia in wild-type (WT) mice and those with tissue factor (TF) inducibly deleted from lung epithelial cells.

Results: In WT mice, fibrinogen mRNA was induced in the liver and elevated in the blood during pneumonia, while TF mRNA was strongest in lung epithelial cells. Bacteria grew inexorably in the lungs and caused bacteremia, which was not affected by deletion of TF from the lung epithelium. However, deletion of lung epithelial cell TF reduced alveolar fibrin deposition and neutrophil recruitment. While Sp infection caused alveolar necrosis in WT mice, we instead observed type II epithelial cell hyperplasia when TF was deleted from the lung epithelium.

Conclusion: The airspace fibrin, neutrophil accumulation, and epithelial necrosis that are defining features of necrosuppurative pneumonia caused by severe pneumococcal infection all depend on TF produced by lung epithelial cells.