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ERJ Open Res. 2018 Mar 23;4(1). pii: 00130-2017. doi: 10.1183/23120541.00130-2017. eCollection 2018 Jan.

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

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Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Joint first authors.
Dept of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia.
The Prince Charles Hospital, Brisbane, Australia.
The University of Newcastle, Newcastle, Australia.
Child Health Division, Menzies School of Health Research, Charles Darwin Hospital, Darwin, Australia.
Institute for Molecular Bioscience, Brisbane, Australia.
Dept of Medicine, The University of Adelaide, Adelaide, Australia.
Respiratory and Sleep Medicine, Lady Cilento Children's Hospital and Children's Centre for Health Research, Queensland University of Technology, Brisbane, Australia.
Wesley Hospital, Brisbane, Australia.
School of Nursing and Midwifery, Menzies Health Institute Queensland, Griffith University, Brisbane, Australia.
Queensland University of Technology, Brisbane, Australia.
Joint senior authors.


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.

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