Alveolar macrophage in protracted bacterial bronchitis

Abstract

Background: Protracted bacterial bronchitis (PBB) is characterised by chronic wet cough in young children and isolation of bacteria such as nontypeable Haemophilus influenza (NTHi). Some children with PBB are thought to develop bronchiectasis but there is a paucity of information available on the pathogenesis of PBB and the factors associated with persistent bacterial infection. Aims: To characterise alveolar macrophage in PBB airways, and to determine whether endotoxin tolerance plays a role in PBB pathophysiology. Results: Alveolar macrophages in the PBB airways are refractory to further in vitro stimulation of NTHi, implicating that the cells are underdoing endotoxin tolerance. BAL cells from the PBB airways (n=15) express lower expression of infection response associated marker MARCO (3-fold) , PPAR- g (3-fold) and TREM2 (3-fold) compared to BAL cells from healthy children (n=7). Expression of RelB , a transcription factor involved in endotoxin tolerance, was increased in PBB BAL cell (6-fold). Higher level of the M1 associated chemokine CCL20 (7-fold) and a trend for increased expression of CCL3, and cytokine, TNF- a was detected in PBB BAL cells. However, the PBB BALs cells also express higher level of the M2 associated cytokine IL-10 (5-fold), and M2 associated marker CD200R (3-fold). Conclusions: Our findings suggest that the thermostat for macrophage activation may be set high in PBB, and this may explain why these children are vulnerable to NTHi and other bacterial infections. Activation of RelB transcription factor in PBB airway cells provided evidence of endotoxin tolerance in these cells. Whether or not gene expression patterns fit neatly into traditional M1 and M2 macrophage subsets remains unclear at this stage.