PT - JOURNAL ARTICLE AU - Alice C-H. Chen AU - Hai B. Tran AU - Yang Xi AU - Stephanie T. Yerkovich AU - Katherine J. Baines AU - Susan J. Pizzutto AU - Melanie Carroll AU - Avril A.B. Robertson AU - Matthew A. Cooper AU - Kate Schroder AU - Jodie L. Simpson AU - Peter G. Gibson AU - Greg Hodge AU - Ian B. Masters AU - Helen M. Buntain AU - Helen L. Petsky AU - Samantha J. Prime AU - Anne B. Chang AU - Sandra Hodge AU - John W. Upham TI - Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis AID - 10.1183/23120541.00130-2017 DP - 2018 Jan 01 TA - ERJ Open Research PG - 00130-2017 VI - 4 IP - 1 4099 - http://openres.ersjournals.com/content/4/1/00130-2017.short 4100 - http://openres.ersjournals.com/content/4/1/00130-2017.full SO - erjor2018 Jan 01; 4 AB - Protracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1β expression and infection, often with nontypeable Haemophilus influenzae (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood.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.In healthy adult PBMCs, CD14+ monocytes contributed to 95% of total IL-1β-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1β expression (p<0.001), but decreased NLRC4 expression (p<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.We conclude that both the NLRP3 and AIM2 inflammasomes probably drive the IL-1β-dominated inflammation in PBB.Airway IL-1β activation in protracted bacterial bronchitis http://ow.ly/ut9r30iqim2