This project builds on our recent findings about certain type of immune cells known as macrophages. Our research found that macrophages in the lungs of children with protracted bacterial bronchitis appear functionally paralysed relative to macrophages from healthy children, with reduced capacity to respond to bacterial challenge. The aim of this study is to develop a molecular signature of that macrophage dysfunction that can be applied to stored lung samples from Indigenous children with chronic suppurative lung disease and bronchiectasis. We can then use this molecular signature to determine if macrophage dysfunction predicts clinical outcomes in children with protracted bacterial bronchitis which may help us predict those children who will have the worst outcomes.
Macrophages from children with PBB and bronchiectasis showed differential gene expression of CCL20, MARCO, CCL24, IL-10, PPAR-γ, CD200R, TREM2, RelB. Several of these genes are involved in the resolution of inflammation and anti-inflammation response, and were associated the bacterial pathogen load identified in the lungs. Together this suggests that lung macrophage dysfunction in PBB and bronchiectasis may contribute to poor bacterial clearance and prolonged resolution of inflammation.
Pediatr Pulmonol. 2018;53(5):575-582
ERJ Open Res 2018;4(1) pii: 00130-2017
ERJ Open Res 2017;3(4) pii: 00025-2017