Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide.
Respir Res
; 22(1): 263, 2021 Oct 10.
Article
in En
| MEDLINE
| ID: mdl-34629055
ABSTRACT
BACKGROUND:
Inhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic mold Aspergillus niger (A. niger).METHODS:
C57BL/6J mice were intranasally challenged with the viable spores of A. niger with and without 1 µg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined.RESULTS:
In comparison to mice challenged only with A. niger, addition of LPS (1 µg) to A. niger abrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and TH2 responses while enhancing TH1 and TH17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies.CONCLUSIONS:
In contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aspergillus niger
/
Spores, Fungal
/
Lipopolysaccharides
/
Bronchial Hyperreactivity
/
Pulmonary Aspergillosis
/
Alveolitis, Extrinsic Allergic
/
Lung
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Respir Res
Year:
2021
Type:
Article
Affiliation country:
China