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Surfactant protein-A-deficient mice are susceptible to Pseudomonas aeruginosa infection
A M LeVine1, K E Kurak, M D Bruno
1Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Abstract:
To determine the role of surfactant protein-A (SP-A) in host defense, the murine SP-A locus was targeted by homologous recombination to produce mice lacking SP-A. SP-A-/- and wild-type mice were infected with mucoid Pseudomonas aeruginosa by intratracheal instillation. Pulmonary bacterial loads were greater in SP-A-/- than in wild-type mice, with increased numbers of mucoid P. aeruginosa in lung homogenates at 6 and 24 h after infection. Pulmonary infiltration with polymorphonuclear leukocytes (PMN) was similar in both groups; however, an earlier influx of PMN into the lung occurred in the SP-A-/- mice. The number of bacteria phagocytosed by alveolar macrophages was decreased in the SP-A-/- mice at 1 h after infection. Superoxide-radical generation by PMN was similar for the SP-A-/- and wild-type mice, but nitrite levels were increased in SP-A-/- mice. Concentrations of tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2 (proinflammatory cytokines) were greater in bronchoalveolar lavage fluid at 2 h after infection in SP-A-/- mice. SP-A plays an important role in the pathogenesis of mucoid P. aeruginosa infection in the lung in vivo by enhancing macrophage phagocytosis and clearance of bacteria, and by modifying the inflammatory response.
Insights
Surfactant protein-A (SP-A) is crucial for host defense against Pseudomonas aeruginosa lung infections. Mice lacking SP-A showed impaired bacterial clearance and altered inflammatory responses.
Area of Science:
- Pulmonary immunology
- Host-pathogen interactions
- Innate immunity
Background:
- Surfactant protein-A (SP-A) is a key component of the innate immune system in the lungs.
- Its precise role in host defense against bacterial lung infections remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of SP-A in host defense against mucoid Pseudomonas aeruginosa lung infection.
- To analyze the impact of SP-A deficiency on bacterial clearance, inflammatory cell recruitment, and cytokine production in vivo.
Main Methods:
- Generation of SP-A knockout (SP-A-/-) mice using homologous recombination.
- Intratracheal instillation of mucoid Pseudomonas aeruginosa in SP-A-/- and wild-type mice.
- Quantification of pulmonary bacterial loads, inflammatory cell infiltration (PMN), macrophage phagocytosis, and levels of inflammatory mediators (cytokines, nitrite).
Main Results:
- SP-A-/- mice exhibited significantly higher pulmonary bacterial loads compared to wild-type mice at 6 and 24 hours post-infection.
- Macrophage phagocytosis of bacteria was reduced in SP-A-/- mice.
- An earlier influx of polymorphonuclear leukocytes (PMN) into the lungs was observed in SP-A-/- mice, along with increased levels of proinflammatory cytokines and nitrite.
Conclusions:
- SP-A plays a critical role in host defense against mucoid Pseudomonas aeruginosa lung infections.
- SP-A enhances macrophage phagocytosis and bacterial clearance.
- SP-A modulates the pulmonary inflammatory response during infection.