| First Author | Tabeling C | Year | 2021 |
| Journal | Am J Physiol Lung Cell Mol Physiol | PubMed ID | 33655757 |
| Mgi Jnum | J:304898 | Mgi Id | MGI:6515314 |
| Doi | 10.1152/ajplung.00505.2020 | Citation | Tabeling C, et al. (2021) Pulmonary fibrosis in Fra-2 transgenic mice is associated with decreased numbers of alveolar macrophages and increased susceptibility to pneumococcal pneumonia. Am J Physiol Lung Cell Mol Physiol |
| abstractText | INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a deadly condition characterized by progressive respiratory dysfunction. Exacerbations due to airway infections are believed to promote disease progression, and presence of Streptococcus in the lung microbiome has been associated with progression of IPF and mortality. The aim of this study was to analyze the effect of lung fibrosis on susceptibility to pneumococcal pneumonia and bacteremia. METHODS: The effects of subclinical (low dose) infection with Streptococcus pneumoniae were studied in a well characterized fos-related antigen-2 (Fra-2) transgenic (TG) mouse model of spontaneous, progressive pulmonary fibrosis. Forty-eight hours after transnasal infection with Streptococcus pneumoniae, bacterial load was assessed in lung tissue, bronchoalveolar lavage (BAL), blood and spleen. Leukocyte subsets and cytokine levels were analyzed in BAL and blood. Lung compliance and arterial blood gases were assessed. RESULTS: In contrast to wildtype mice, low dose lung infection with Streptococcus pneumoniae in Fra-2 TG mice resulted in substantial pneumonia including weight loss, increased lung bacterial load and bacteremia. BAL alveolar macrophages were reduced in Fra-2 TG mice compared to the corresponding WT mice. Proinflammatory cytokines and chemokines (IL-1beta, IL-6, TNF-alpha, CXCL1) were elevated upon infection in BAL supernatant and plasma of Fra-2 TG mice. Lung compliance was decreased in Fra-2 TG mice following low dose infection with Streptococcus pneumoniae. CONCLUSIONS: Pulmonary fibrosis increases susceptibility to pneumococcal pneumonia and bacteremia possibly via impaired alveolar bacterial clearance. |
