Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β

Alice C.H. Chen, Yang Xi, Melanie Carroll, Helen L. Petsky, Samantha J. Gardiner, Susan J. Pizzutto, Stephanie T. Yerkovich, Katherine J. Baines, Peter G. Gibson, Sandra Hodge, Ian B. Masters, Helen M. Buntain, Anne B. Chang, John W. Upham

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Abstract

Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHistimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+T cells and CD56+NK cells. Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.

Original languageEnglish
Article number00025-2017
Pages (from-to)1-10
Number of pages10
JournalERJ Open Research
Volume3
Issue number4
DOIs
Publication statusPublished - 1 Oct 2017

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Interleukin-1
Bronchitis
Bronchiectasis
Cytokines
Rhinovirus
Blood Cells
Haemophilus influenzae
Interferons
Inflammation
Interleukin-1 Receptors
Interleukins
Cough
Cellular Immunity
Natural Killer Cells
Interleukin-10
Immunity
Interleukin-6
T-Lymphocytes

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Chen, A. C. H., Xi, Y., Carroll, M., Petsky, H. L., Gardiner, S. J., Pizzutto, S. J., ... Upham, J. W. (2017). Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β. ERJ Open Research, 3(4), 1-10. [00025-2017]. https://doi.org/10.1183/23120541.00025-2017
Chen, Alice C.H. ; Xi, Yang ; Carroll, Melanie ; Petsky, Helen L. ; Gardiner, Samantha J. ; Pizzutto, Susan J. ; Yerkovich, Stephanie T. ; Baines, Katherine J. ; Gibson, Peter G. ; Hodge, Sandra ; Masters, Ian B. ; Buntain, Helen M. ; Chang, Anne B. ; Upham, John W. / Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β. In: ERJ Open Research. 2017 ; Vol. 3, No. 4. pp. 1-10.
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title = "Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β",
abstract = "Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHistimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+T cells and CD56+NK cells. Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.",
author = "Chen, {Alice C.H.} and Yang Xi and Melanie Carroll and Petsky, {Helen L.} and Gardiner, {Samantha J.} and Pizzutto, {Susan J.} and Yerkovich, {Stephanie T.} and Baines, {Katherine J.} and Gibson, {Peter G.} and Sandra Hodge and Masters, {Ian B.} and Buntain, {Helen M.} and Chang, {Anne B.} and Upham, {John W.}",
year = "2017",
month = "10",
day = "1",
doi = "10.1183/23120541.00025-2017",
language = "English",
volume = "3",
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Chen, ACH, Xi, Y, Carroll, M, Petsky, HL, Gardiner, SJ, Pizzutto, SJ, Yerkovich, ST, Baines, KJ, Gibson, PG, Hodge, S, Masters, IB, Buntain, HM, Chang, AB & Upham, JW 2017, 'Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β', ERJ Open Research, vol. 3, no. 4, 00025-2017, pp. 1-10. https://doi.org/10.1183/23120541.00025-2017

Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β. / Chen, Alice C.H.; Xi, Yang; Carroll, Melanie; Petsky, Helen L.; Gardiner, Samantha J.; Pizzutto, Susan J.; Yerkovich, Stephanie T.; Baines, Katherine J.; Gibson, Peter G.; Hodge, Sandra; Masters, Ian B.; Buntain, Helen M.; Chang, Anne B.; Upham, John W.

In: ERJ Open Research, Vol. 3, No. 4, 00025-2017, 01.10.2017, p. 1-10.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β

AU - Chen, Alice C.H.

AU - Xi, Yang

AU - Carroll, Melanie

AU - Petsky, Helen L.

AU - Gardiner, Samantha J.

AU - Pizzutto, Susan J.

AU - Yerkovich, Stephanie T.

AU - Baines, Katherine J.

AU - Gibson, Peter G.

AU - Hodge, Sandra

AU - Masters, Ian B.

AU - Buntain, Helen M.

AU - Chang, Anne B.

AU - Upham, John W.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHistimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+T cells and CD56+NK cells. Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.

AB - Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHistimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+T cells and CD56+NK cells. Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.

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