Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide
© 2021. The Author(s)..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2021 |
---|---|
Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
---|---|
Enthalten in: |
Respiratory research - 22(2021), 1 vom: 10. Okt., Seite 263 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Zeng, Yuying [VerfasserIn] |
---|
Links: |
---|
Themen: |
Acute hypersensitivity pneumonitis |
---|
Anmerkungen: |
Date Completed 14.02.2022 Date Revised 26.02.2024 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.1186/s12931-021-01850-5 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM331699966 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM331699966 | ||
003 | DE-627 | ||
005 | 20240229153836.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2021 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1186/s12931-021-01850-5 |2 doi | |
028 | 5 | 2 | |a pubmed24n1306.xml |
035 | |a (DE-627)NLM331699966 | ||
035 | |a (NLM)34629055 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Zeng, Yuying |e verfasserin |4 aut | |
245 | 1 | 0 | |a Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide |
264 | 1 | |c 2021 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 14.02.2022 | ||
500 | |a Date Revised 26.02.2024 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2021. The Author(s). | ||
520 | |a 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) | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Acute hypersensitivity pneumonitis | |
650 | 4 | |a Fungi | |
650 | 4 | |a LPS | |
650 | 4 | |a TH1, TH2, TH17 response | |
650 | 7 | |a Lipopolysaccharides |2 NLM | |
700 | 1 | |a Zhang, Yun |e verfasserin |4 aut | |
700 | 1 | |a Huang, Xinyan |e verfasserin |4 aut | |
700 | 1 | |a Song, Lizhen |e verfasserin |4 aut | |
700 | 1 | |a Polsky, Katherine |e verfasserin |4 aut | |
700 | 1 | |a Wu, Yifan |e verfasserin |4 aut | |
700 | 1 | |a Kheradmand, Farrah |e verfasserin |4 aut | |
700 | 1 | |a Guo, Yubiao |e verfasserin |4 aut | |
700 | 1 | |a Green, Linda K |e verfasserin |4 aut | |
700 | 1 | |a Corry, David B |e verfasserin |4 aut | |
700 | 1 | |a Knight, John M |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Respiratory research |d 2000 |g 22(2021), 1 vom: 10. Okt., Seite 263 |w (DE-627)NLM115627553 |x 1465-993X |7 nnns |
773 | 1 | 8 | |g volume:22 |g year:2021 |g number:1 |g day:10 |g month:10 |g pages:263 |
856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12931-021-01850-5 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 22 |j 2021 |e 1 |b 10 |c 10 |h 263 |