Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice

To determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc(-/-)) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection. Survival of young, postnatal day 14 Sftpc(-/-) mice was decreased in comparison to Sftpc(+/+) mice. The sensitivity to Pseudomonas bacteria was specific to the 129S6 strain of Sftpc(-/-) mice, a strain that spontaneously develops interstitial lung disease-like lung pathology with age. Pulmonary bacterial load and leukocyte infiltration were increased in the lungs of Sftpc(-/-) mice 24 h after infection. Early influx of polymorphonuclear leukocytes in the lungs of uninfected newborn Sftpc(-/-) mice relative to Sftpc(+/+) mice indicate that the lack of SP-C promotes proinflammatory responses in the lung. Mucin expression, as indicated by Alcian blue staining, was increased in the airways of Sftpc(-/-) mice following infection. Phagocytic activity of alveolar macrophages from Sftpc(-/-) mice was reduced. The uptake of fluorescent beads in vitro and the number of bacteria phagocytosed by alveolar macrophages in vivo was decreased in the Sftpc(-/-) mice. Alveolar macrophages from Sftpc(-/-) mice expressed markers of alternative activation that are associated with diminished pathogen response and advancing pulmonary fibrosis. These findings implicate SP-C as a modifier of alveolar homeostasis. SP-C plays an important role in innate host defense of the lung, enhancing macrophage-mediated Pseudomonas phagocytosis, clearance and limiting pulmonary inflammatory responses.