Enhanced Susceptibility to Pulmonary Infection withBurkholderia cepaciainCftr−/−Mice
| Autor: | Carola Sjolin, Brent Steer, Annie Lu, Geraldine Kent, Gregory P. Downey, Yi Jun Wu, Janet F. Forstner, Vera Cherapanov, George Thanassoulis, Colin McKerlie, Uma Sajjan, Ori D. Rotstein |
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| Rok vydání: | 2001 |
| Předmět: |
Immunology
Population Cystic Fibrosis Transmembrane Conductance Regulator Burkholderia cepacia Lung injury Microbiology Cystic fibrosis Mice Bronchopneumonia medicine Animals Cyclic AMP Response Element-Binding Protein education Lung Mice Knockout education.field_of_study medicine.diagnostic_test biology Respiratory disease NF-kappa B Burkholderia Infections Bacterial Infections Macrophage Activation respiratory system medicine.disease Cystic fibrosis transmembrane conductance regulator respiratory tract diseases Pneumonia Infectious Diseases Bronchoalveolar lavage medicine.anatomical_structure biology.protein Cytokines Parasitology Disease Susceptibility Bronchoalveolar Lavage Fluid |
| Zdroj: | Infection and Immunity. 69:5138-5150 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.69.8.5138-5150.2001 |
| Popis: | Progressive pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the molecular basis for this susceptibility remains incompletely understood. To study this problem, we developed a model of chronic pneumonia by repeated instillation of a clinical isolate ofBurkholderia cepacia(genomovar III, ET12 strain), an opportunistic gram-negative bacterium, from a case of CF into the lungs ofCftrm1unc−/−(Cftr−/−) and congenicCftr+/+controls. Nine days after the last instillation, the CF transmembrane regulator knockout mice showed persistence of viable bacteria with chronic severe bronchopneumonia while wild-type mice remained healthy. The histopathological changes in the lungs of the susceptibleCftr−/−mice were characterized by infiltration of a mixed inflammatory-cell population into the peribronchiolar and perivascular spaces, Clara cell hyperplasia, mucus hypersecretion in airways, and exudation into alveolar airspaces by a mixed population of macrophages and neutrophils. An increased proportion of neutrophils was observed in bronchoalveolar lavage fluid from theCftr−/−mice, which, despite an increased bacterial load, demonstrated minimal evidence of activation. Alveolar macrophages fromCftr−/−mice also demonstrated suboptimal activation. These observations suggest that the pulmonary host defenses are compromised in lungs from animals with CF, as manifested by increased susceptibility to bacterial infection and lung injury. This murine model of chronic pneumonia thus reflects, in part, the situation in human patients and may help elucidate the mechanisms leading to defective host defense in CF. |
| Databáze: | OpenAIRE |
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