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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β
Alice C-H Chen1,2, Yang Xi1,2, Melanie Carroll1
1Diamantina Institute, The University of Queensland, Brisbane, Australia.
Insights
Interleukin-1 beta (IL-1β) significantly influences immune responses in children with protracted bacterial bronchitis (PBB) and bronchiectasis. Blocking IL-1β may reduce airway inflammation but could compromise immunity against common respiratory pathogens.
Area of Science:
- Immunology
- Pediatric Respiratory Medicine
- Infectious Diseases
Background:
- Protracted bacterial bronchitis (PBB) and bronchiectasis share neutrophilic airway inflammation and an interleukin-1 beta (IL-1β) signature.
- The role of the IL-1β pathway in host defense against respiratory pathogens in children is not fully understood.
Purpose of the Study:
- To compare systemic immune responses to common pathogens in children with PBB, bronchiectasis, and healthy controls.
- To investigate the importance of the IL-1β pathway in these immune responses.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from children with PBB, bronchiectasis, and controls were stimulated with non-typeable Haemophilus influenzae (NTHi).
- The effect of an IL-1 receptor antagonist (IL-1Ra) on cytokine production was assessed in NTHi- and rhinovirus-stimulated PBMCs.
- Cellular responses were analyzed across various immune cell types, including T cells and NK cells.
Main Results:
- NTHi stimulation induced high levels of IL-1β, IL-6, interferon-gamma (IFN-γ), and IL-10 in PBMCs from all groups.
- Blocking IL-1β with IL-1Ra inhibited cytokine synthesis in response to NTHi and rhinovirus.
- IL-1Ra significantly reduced IFN-γ production by T cells and NK cells.
Conclusions:
- IL-1β plays a crucial role in regulating cellular immune responses to NTHi and rhinovirus in children.
- While targeting the IL-1β pathway may reduce airway inflammation, it could potentially impair protective immunity against these pathogens.
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 NTHi-stimulated 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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