Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia.
Diamantina Institute, The University of Queensland, Brisbane, Australia.
Pediatr Pulmonol. 2018 May;53(5):575-582. doi: 10.1002/ppul.23984. Epub 2018 Mar 24.
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.
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.
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.
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.
迁延性细菌性支气管炎(PBB)是小儿慢性咳嗽的常见病因,可能是支气管扩张的前兆。细菌常存在于 PBB 和支气管扩张的下呼吸道,可能引起持续感染。然而,目前关于 PBB 的发病机制以及与持续细菌感染和进展为支气管扩张相关的因素的信息有限。本研究假设,与对照受试者的肺免疫细胞相比,复发性 PBB 和支气管扩张中的肺免疫细胞差异表达与免疫细胞功能障碍相关的基因。
从支气管肺泡灌洗液(成人对照和 PBB BAL 细胞)中分离细胞,用非分型流感嗜血杆菌(NTHi)刺激,并评估参与各种炎症途径的基因表达。
NTHi 诱导成人对照 BAL 细胞大量产生 IL-1β、IL-6 和 IL-8,但 PBB 气道的 BAL 细胞似乎对 NTHi 刺激无反应。与对照细胞相比,PBB 和支气管扩张的 BAL 细胞显示出几个基因的差异表达,包括 CCL20、MARCO、CCL24、IL-10、PPAR-γ、CD200R、TREM2、RelB。参与炎症消退和抗炎反应的基因表达,如 CD200R 和 IL-10,与气道中发现的致病性细菌数量有关。
总之,我们已经表明,与巨噬细胞功能和炎症消退相关的基因表达在 PBB 和支气管扩张中相似。PBB 和支气管扩张中的肺免疫细胞功能障碍可能导致细菌清除不良和炎症消退延长。