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Published on: April 14, 2010
Airway cells from protracted bacterial bronchitis and bronchiectasis share similar gene expression profiles
Alice C-H Chen1,2, Olga M Pena1, Hendrik J Nel2
1Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia.
Insights
Immune cells in protracted bacterial bronchitis (PBB) and bronchiectasis show impaired responses to bacteria, contributing to persistent infections. Gene expression analysis reveals dysfunction in lung immune cells, hindering bacterial clearance and inflammation resolution.
Area of Science:
- Pediatric Pulmonology
- Immunology
- Microbiology
Background:
- Protracted bacterial bronchitis (PBB) is a common cause of chronic cough in children and may precede bronchiectasis.
- Persistent bacterial infections in the lower airways are implicated in both PBB and bronchiectasis.
- The pathogenesis of PBB and factors driving progression to bronchiectasis remain poorly understood.
Purpose of the Study:
- To investigate gene expression differences in lung immune cells from children with recurrent PBB and bronchiectasis compared to controls.
- To explore the role of immune cell dysfunction in persistent bacterial infections and disease progression.
Main Methods:
- Bronchoalveolar lavage (BAL) cells were isolated from adult controls and children with PBB.
- BAL cells were stimulated with nontypeable Haemophilus influenzae (NTHi).
- Gene expression related to inflammatory pathways was assessed using quantitative PCR.
Main Results:
- BAL cells from PBB airways were refractory to NTHi stimulation, unlike control cells which produced significant IL-1β, IL-6, and IL-8.
- Differential gene expression was observed in PBB and bronchiectasis BAL cells compared to controls, including genes involved in inflammation (CCL20, MARCO, CCL24) and immune regulation (IL-10, PPAR-γ, CD200R, TREM2, RelB).
- Genes associated with anti-inflammatory responses (CD200R, IL-10) correlated with bacterial load.
Conclusions:
- Lung immune cells in PBB and bronchiectasis exhibit similar gene expression patterns related to macrophage function and inflammation resolution.
- Immune cell dysfunction in PBB and bronchiectasis likely impairs bacterial clearance and prolongs inflammation, potentially contributing to disease progression.
Aim:
Protracted bacterial bronchitis (PBB) is a common cause of prolonged cough in young children, and may be a precursor of bronchiectasis. Bacteria are often present in the lower airways in both PBB and bronchiectasis and may cause persistent infections. However, there is a paucity of information available on the pathogenesis of PBB and the factors associated with persistent bacterial infection and progression to bronchiectasis. This study hypothesised that lung immune cells in recurrent PBB and bronchiectasis differentially express genes related to immune cell dysfunction compared to lung immune cells from control subjects.
Method:
Cells isolated from bronchoalveolar lavage (adult-control and PBB BAL cells) were stimulated with nontypeable Haemophilus influenzae (NTHi), and expression of genes involved in various inflammatory pathways was assessed.
Result:
NTHi induced production of large amounts of IL-1β, IL-6, and IL-8 in adult-control BAL cells, however BAL cells from PBB airways appeared refractory to NTHi stimulation. BAL cells from PBB and bronchiectasis showed differential expression of several genes relative to control cells, including CCL20, MARCO, CCL24, IL-10, PPAR-γ, CD200R, TREM2, RelB. Expression of genes involved in resolution of inflammation and anti-inflammation response, such as CD200R and IL-10, was associated with the number of pathogenic bacteria found in the airways.
Conclusion:
In summary, we have shown that the expression of genes related to macrophage function and resolution of inflammation are similar in PBB and bronchiectasis. Lung immune cell dysfunction in PBB and bronchiectasis may contribute to poor bacterial clearance and prolonged resolution of inflammation.
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