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

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Chen, Alice C-H
Tran, Hai B
Xi, Yang
Yerkovich, Stephanie T
Baines, Katherine J
Pizzutto, Susan J
Carroll, Melanie
Robertson, Avril AB
Cooper, Matthew A
Schroder, Kate
Simpson, Jodie L
Gibson, Peter G
Hodge, Greg
Masters, Ian B
Buntain, Helen M
Petsky, Helen L
Prime, Samantha J
Chang, Anne B
Hodge, Sandra
Upham, John W
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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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ERJ Open Research

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© ERS 2018. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0 (, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.

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Respiratory diseases

Medical bacteriology

Biomedical and clinical sciences

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Chen, AC-H; Tran, HB; Xi, Y; Yerkovich, ST; Baines, KJ; Pizzutto, SJ; Carroll, M; Robertson, AAB; Cooper, MA; Schroder, K; Simpson, JL; Gibson, PG; Hodge, G; Masters, IB; Buntain, HM; Petsky, HL; Prime, SJ; Chang, AB; Hodge, S; Upham, JW, Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis., ERJ Open Research, 2018, 4 (1), pp. 1-11