Pulmonary fibrosis in mice increases susceptibility to pneumococcal pneumonia and bacteremia

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition characterized by progressively deteriorating respiratory function. Exacerbations due to lung infections are thought to promote disease progression, and the presence of Streptococcus in the lung microbiome has been linked to progression of IPF. The aim of this study was to evaluate the impact of pulmonary fibrosis on susceptibility to pneumococcal pneumonia and subsequent bacteremia. Methods: The effect of subclinical low-dose infection with Streptococcus pneumoniae via the nasal route was studied using fos-related antigen-2 (Fra-2) transgenic (TG) mice, which develop spontaneous progressive pulmonary fibrosis. Two days after infection bacterial load was assessed in lung tissue, bronchoalveolar lavage (BAL), blood and spleen. Leukocyte subsets and cytokine levels were analyzed in BAL and blood. Additionally, lung compliance and arterial blood gases were assessed. Results: 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, whereas WT mice remained mostly unaffected. Compared to WT mice BAL alveolar macrophages were reduced in Fra-2 TG mice. Proinflammatory cytokines and chemokines were elevated upon infection in BAL supernatant and plasma of Fra-2 TG mice. Following infection lung compliance was decreased in Fra-2 TG mice. Conclusion: Pulmonary fibrosis increases susceptibility to pneumococcal pneumonia and bacteremia possibly via impaired alveolar bacterial clearance.