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Mucociliary clearance in cystic fibrosis knockout mice infected with Pseudomonas aeruginosa
E A Cowley1, C G Wang, D Gosselin
1Montreal Chest Institute Research Centre, Royal Victoria Hospital, McGill University, Quebec, Canada.
Abstract:
In this study, we examined whether mucociliary clearance differed between cystic fibrosis (CF) knockout mice and wildtype controls. Additionally, we investigated whether infection with Pseudomonas aeruginosa, a common pathogen in the CF lung, affected this important host defence mechanism. Ciliary beat frequency (fcb) and particle transport (PT) were recorded using an in vitro lung explant preparation. Measurements were made from uninfected cystic fibrosis transmembrane conductance regulator (CFTR) knockout (-/-) mice and littermate controls (+/+) and compared to measurements from infected animals. While there were no differences detectable in fcb between CFTR -/- mice and their +/+ controls either in the presence or absence of P. aeruginosa, PT rates were different between these groups; interestingly, PT rates appeared dependent on both CFTR and infection status, with uninfected CFTR +/+ animals demonstrating higher rates of PT than their -/- littermates, while CFTR +/+ P. aeruginosa-infected mice demonstrated lower PT than knockout mice. These data demonstrate differences in mucociliary clearance between cystic fibrosis transmembrane conductance regulator knockout mice and controls, and further that Pseudomonas aeruginosa infection affects mucociliary clearance in the peripheral airways of mice. Additionally, the observed differences in particle transport suggest that cystic fibrosis transmembrane conductance regulator knockout mice demonstrate different mucociliary responses to infection.
Insights
Mucociliary clearance, a key lung defense, differs in cystic fibrosis (CF) mice. Pseudomonas aeruginosa infection further alters particle transport in CFTR knockout mice, impacting lung health.
Area of Science:
- Pulmonary Medicine
- Genetics
- Microbiology
Background:
- Cystic fibrosis (CF) is a genetic disorder affecting lung function.
- Mucociliary clearance is a critical host defense mechanism in the lungs.
- Pseudomonas aeruginosa infection is common in CF patients and impacts lung health.
Purpose of the Study:
- To investigate differences in mucociliary clearance between CFTR knockout mice and wildtype controls.
- To determine the effect of Pseudomonas aeruginosa infection on mucociliary clearance in CFTR knockout mice.
Main Methods:
- In vitro lung explant preparation was used to measure ciliary beat frequency (fcb) and particle transport (PT).
- Measurements were taken from both uninfected and P. aeruginosa-infected CFTR knockout mice and wildtype littermate controls.
Main Results:
- No significant differences in ciliary beat frequency were observed between CFTR knockout and wildtype mice, with or without P. aeruginosa infection.
- Particle transport rates differed significantly between groups, influenced by both CFTR status and infection.
- Uninfected wildtype mice showed higher PT than uninfected CFTR knockout mice.
- P. aeruginosa-infected wildtype mice exhibited lower PT than infected CFTR knockout mice.
Conclusions:
- Mucociliary clearance, specifically particle transport, is impaired in CFTR knockout mice compared to controls.
- Pseudomonas aeruginosa infection differentially affects mucociliary clearance in the peripheral airways of wildtype and CFTR knockout mice.
- CFTR knockout mice display altered mucociliary responses to P. aeruginosa infection, highlighting disease-specific mechanisms.