Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis

<jats:p>Protracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1β expression and infection, often with nontypeable <jats:italic>Haemophilus influenzae</jats:italic> (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood.</jats:p><jats:p>We hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2 inflammasome/IL-1β axis. Lung macrophages obtained from bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte-derived macrophages from patients with PBB and age-matched healthy controls were cultured in control medium or exposed to live NTHi.</jats:p><jats:p>In healthy adult PBMCs, CD14<jats:sup>+</jats:sup> monocytes contributed to 95% of total IL-1β-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased <jats:italic>IL-1β</jats:italic> expression (p&lt;0.001), but decreased <jats:italic>NLRC4</jats:italic> expression (p&lt;0.01). NTHi induced IL-1β secretion in PBMCs from both healthy controls and patients with recurrent PBB. This was inhibited by Z-YVAD-FMK (a caspase-1 selective inhibitor) and by MCC950 (a NLRP3 selective inhibitor). In PBB BAL macrophages inflammasome complexes were visualised as fluorescence specks of NLRP3 or AIM2 colocalised with cleaved caspase-1 and cleaved IL-1β. NTHi stimulation induced formation of specks of cleaved IL-1β, NLRP3 and AIM2 in PBMCs, blood monocytes and monocyte-derived macrophages.</jats:p><jats:p>We conclude that both the NLRP3 and AIM2 inflammasomes probably drive the IL-1β-dominated inflammation in PBB.</jats:p>