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

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

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    Abstract

    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.
    Original languageEnglish
    Pages (from-to)1-11
    Number of pages11
    JournalEuropean Respiratory Journal
    Volume4
    Issue number1
    DOIs
    Publication statusPublished - 2018

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    Inflammasomes
    Bronchitis
    Interleukin-1
    Haemophilus influenzae
    Inflammation
    Blood Cells
    Macrophages
    Monocytes
    Bronchoalveolar Lavage
    Caspase 1
    Cough
    Fluorescence
    Lung

    Cite this

    Chen , Alice C-H ; Tran, Hai B. ; Xi , Yang ; Yerkovich, Stephanie ; J. Baines, Katherine ; Pizzutto, Susan ; Carroll, Melanie ; Robertson, Avril A.B. ; 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 ; Hodge, Sandra ; Upham, John W. / Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis. In: European Respiratory Journal. 2018 ; Vol. 4, No. 1. pp. 1-11.
    @article{1730e5e9ff914eedbdae18a66d2c59fd,
    title = "Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis",
    abstract = "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.",
    author = "Chen, {Alice C-H} and Tran, {Hai B.} and Yang Xi and Stephanie Yerkovich and {J. Baines}, Katherine and Susan Pizzutto and Melanie Carroll and Robertson, {Avril A.B.} and Cooper, {Matthew A.} and Kate Schroder and Simpson, {Jodie L.} and Gibson, {Peter G.} and Greg Hodge and Masters, {Ian B.} and Buntain, {Helen M.} and Petsky, {Helen L.} and Prime, {Samantha J.} and Anne Chang and Sandra Hodge and Upham, {John W.}",
    year = "2018",
    doi = "10.1183/23120541.00130-2017",
    language = "English",
    volume = "4",
    pages = "1--11",
    journal = "European Respiratory Journal",
    issn = "0903-1936",
    publisher = "Unknown",
    number = "1",

    }

    Chen , AC-H, Tran, HB, Xi , Y, Yerkovich, S, J. Baines, K, Pizzutto, S, Carroll, M, Robertson, AAB, Cooper, MA, Schroder, K, Simpson, JL, Gibson, PG, Hodge, G, Masters, IB, Buntain, HM, Petsky, HL, Prime, SJ, Chang, A, Hodge, S & Upham, JW 2018, 'Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis', European Respiratory Journal, vol. 4, no. 1, pp. 1-11. https://doi.org/10.1183/23120541.00130-2017

    Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis. / Chen , Alice C-H; Tran, Hai B. ; Xi , Yang; Yerkovich, Stephanie; J. Baines, Katherine ; Pizzutto, Susan; Carroll, Melanie; Robertson, Avril A.B. ; 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; Hodge, Sandra; Upham, John W.

    In: European Respiratory Journal, Vol. 4, No. 1, 2018, p. 1-11.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis

    AU - Chen , Alice C-H

    AU - Tran, Hai B.

    AU - Xi , Yang

    AU - Yerkovich, Stephanie

    AU - J. Baines, Katherine

    AU - Pizzutto, Susan

    AU - Carroll, Melanie

    AU - Robertson, Avril A.B.

    AU - Cooper, Matthew A.

    AU - Schroder, Kate

    AU - Simpson, Jodie L.

    AU - Gibson, Peter G.

    AU - Hodge, Greg

    AU - Masters, Ian B.

    AU - Buntain, Helen M.

    AU - Petsky, Helen L.

    AU - Prime, Samantha J.

    AU - Chang, Anne

    AU - Hodge, Sandra

    AU - Upham, John W.

    PY - 2018

    Y1 - 2018

    N2 - 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.

    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.

    U2 - 10.1183/23120541.00130-2017

    DO - 10.1183/23120541.00130-2017

    M3 - Article

    VL - 4

    SP - 1

    EP - 11

    JO - European Respiratory Journal

    JF - European Respiratory Journal

    SN - 0903-1936

    IS - 1

    ER -