- Title
- Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis
- Creator
- Chen, Alice C.-H.; Tran, Hai B.; 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.; Xi, Yang; Yerkovich, Stephanie T.; Baines, Katherine J.; Pizzutto, Susan J.; Carroll, Melanie; Robertson, Avril A. B.; Cooper, Matthew A.; Schroder, Kate
- Relation
- NHMRC.1058213 http://purl.org/au-research/grants/nhmrc/1058213
- Relation
- ERJ Open Research Vol. 4, Issue 1
- Publisher Link
- http://dx.doi.org/10.1183/23120541.00130-2017
- Publisher
- European Respiratory Society
- Resource Type
- journal article
- Date
- 2018
- Description
- Protracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1ß 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-1ß 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-1ß-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1ß expression (p<0.001), but decreased NLRC4 expression (p<0.01). NTHi induced IL-1ß 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-1ß. NTHi stimulation induced formation of specks of cleaved IL-1ß, NLRP3 and AIM2 in PBMCs, blood monocytes and monocyte-derived macrophages. We conclude that both the NLRP3 and AIM2 inflammasomes probably drive the IL-1ß-dominated inflammation in PBB.
- Subject
- airway and lung cell biology; bronchiectasis and primary ciliary dyskinesia; immunology and immunodeficiency; infections; pneumonia; TB; viral; lung pathology; bacterial bronchitis
- Identifier
- http://hdl.handle.net/1959.13/1390091
- Identifier
- uon:32993
- Identifier
- ISSN:2312-0541
- Rights
- © ERS 2018. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
- Language
- eng
- Full Text
- Reviewed
- Hits: 14194
- Visitors: 15142
- Downloads: 371
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 805 KB | Adobe Acrobat PDF | View Details Download |