Abstract | BACKGROUND: OBJECTIVE: The goal of this study was to identify mechanisms underlying bacterial-induced exacerbations by employing LPS as a surrogate for infection. METHODS: We developed a mouse model of LPS-induced exacerbation on the background of pre-existing type-2 allergic airway disease (AAD). RESULTS: LPS-induced exacerbation was characterized by steroid-resistant airway hyperresponsiveness (AHR) and an exaggerated inflammatory response distinguished by increased numbers of infiltrating neutrophils/macrophages and elevated production of lung inflammatory cytokines, including TNFα, IFNγ, IL-27 and MCP-1. Expression of the type-2 associated inflammatory factors such as IL-5 and IL-13 were elevated in AAD but not altered by LPS exposure. Furthermore, AHR and airway inflammation were no longer suppressed by corticosteroid ( dexamethasone) treatment after LPS exposure. Depletion of pulmonary macrophages by administration of 2-chloroadenosine into the lungs suppressed AHR and reduced IL-13, TNFα and IFNγ expression. Blocking IL-13 function, through either IL-13-deficiency or administration of specific blocking antibodies, also suppressed AHR and airway inflammation. CONCLUSIONS & CLINICAL RELEVANCE: We present evidence that IL-13 and innate immune pathways (in particular pulmonary macrophages) contribute to LPS-induced exacerbation of pre-existing AAD and provide insight into the complex molecular processes potentially underlying microbial-induced exacerbations.
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Authors | Sara Hadjigol, Keilah G Netto, Steven Maltby, Hock L Tay, Thi H Nguyen, Nicole G Hansbro, Fiona Eyers, Philip M Hansbro, Ming Yang, Paul S Foster |
Journal | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
(Clin Exp Allergy)
Vol. 50
Issue 1
Pg. 82-94
(01 2020)
ISSN: 1365-2222 [Electronic] England |
PMID | 31579973
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2019 John Wiley & Sons Ltd. |
Chemical References |
- Ccl2 protein, mouse
- Chemokine CCL2
- Cytokines
- Glucocorticoids
- IFNG protein, mouse
- Il27 protein, mouse
- Interleukin-13
- Interleukins
- Lipopolysaccharides
- Muc5ac protein, mouse
- Mucin 5AC
- Tnf protein, mouse
- Tumor Necrosis Factor-alpha
- Dexamethasone
- Interferon-gamma
- Ovalbumin
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Topics |
- Airway Resistance
(drug effects)
- Animals
- Asthma
(immunology)
- Bacterial Infections
- Bronchoalveolar Lavage Fluid
(cytology)
- Chemokine CCL2
- Cytokines
(drug effects, immunology)
- Dexamethasone
(pharmacology)
- Disease Models, Animal
- Disease Progression
- Drug Resistance
- Glucocorticoids
(pharmacology)
- Interferon-gamma
(drug effects, immunology)
- Interleukin-13
(immunology)
- Interleukins
(immunology)
- Lipopolysaccharides
(pharmacology)
- Macrophage Activation
(drug effects, immunology)
- Macrophages, Alveolar
(drug effects, immunology)
- Mice
- Mucin 5AC
(drug effects, metabolism)
- Ovalbumin
- Respiratory Hypersensitivity
(immunology)
- Reverse Transcriptase Polymerase Chain Reaction
- Tumor Necrosis Factor-alpha
(drug effects, immunology)
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