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Novel Mouse Models of Fungal Asthma

Alternaria alternata is a ubiquitous fungus and a major allergen associated with the development of asthma. Inhalation of intact spores is the primary cause of human exposure to fungal allergen. However, allergen-rich cultured fungal filtrates are oftentimes used in the current models of fungal sens...

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Autores principales: Daines, Michael, Pereira, Rhea, Cunningham, Aubrey, Pryor, Barry, Besselsen, David G., Liu, Yuchen, Luo, Qianwen, Chen, Yin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415780/
https://www.ncbi.nlm.nih.gov/pubmed/34485171
http://dx.doi.org/10.3389/fcimb.2021.683194
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author Daines, Michael
Pereira, Rhea
Cunningham, Aubrey
Pryor, Barry
Besselsen, David G.
Liu, Yuchen
Luo, Qianwen
Chen, Yin
author_facet Daines, Michael
Pereira, Rhea
Cunningham, Aubrey
Pryor, Barry
Besselsen, David G.
Liu, Yuchen
Luo, Qianwen
Chen, Yin
author_sort Daines, Michael
collection PubMed
description Alternaria alternata is a ubiquitous fungus and a major allergen associated with the development of asthma. Inhalation of intact spores is the primary cause of human exposure to fungal allergen. However, allergen-rich cultured fungal filtrates are oftentimes used in the current models of fungal sensitization that do not fully reflect real-life exposures. Thus, establishing novel spore exposure models is imperative. In this study, we established novel fungal exposure models of both adult and neonate to live spores. We examined pathophysiological changes in the spore models as compared to the non-exposure controls and also to the conventional filtrate models. While both Alternaria filtrate- and spore-exposed adult BALB/c mice developed elevated airway hyperresponsiveness (AHR), filtrates induced a greater IgE mediated response and higher broncholavage eosinophils than spores. In contrast, the mice exposed to Alternaria spores had higher numbers of neutrophils. Both exposures induced comparable levels of lung tissue inflammation and mucous cell metaplasia (MCM). In the neonatal model, exposure to Alternaria spores resulted in a significant increase of AHR in both adult and neonatal mice. Increased levels of IgE in both neonatal and adult mice exposed to spores was associated with increased eosinophilia in the treatment groups. Adult demonstrated increased numbers of lymphocytes that was paralleled by increased IgG1 production. Both adults and neonates demonstrated similarly increased eosinophilia, IgE, tissue inflammation and MCM.
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spelling pubmed-84157802021-09-04 Novel Mouse Models of Fungal Asthma Daines, Michael Pereira, Rhea Cunningham, Aubrey Pryor, Barry Besselsen, David G. Liu, Yuchen Luo, Qianwen Chen, Yin Front Cell Infect Microbiol Cellular and Infection Microbiology Alternaria alternata is a ubiquitous fungus and a major allergen associated with the development of asthma. Inhalation of intact spores is the primary cause of human exposure to fungal allergen. However, allergen-rich cultured fungal filtrates are oftentimes used in the current models of fungal sensitization that do not fully reflect real-life exposures. Thus, establishing novel spore exposure models is imperative. In this study, we established novel fungal exposure models of both adult and neonate to live spores. We examined pathophysiological changes in the spore models as compared to the non-exposure controls and also to the conventional filtrate models. While both Alternaria filtrate- and spore-exposed adult BALB/c mice developed elevated airway hyperresponsiveness (AHR), filtrates induced a greater IgE mediated response and higher broncholavage eosinophils than spores. In contrast, the mice exposed to Alternaria spores had higher numbers of neutrophils. Both exposures induced comparable levels of lung tissue inflammation and mucous cell metaplasia (MCM). In the neonatal model, exposure to Alternaria spores resulted in a significant increase of AHR in both adult and neonatal mice. Increased levels of IgE in both neonatal and adult mice exposed to spores was associated with increased eosinophilia in the treatment groups. Adult demonstrated increased numbers of lymphocytes that was paralleled by increased IgG1 production. Both adults and neonates demonstrated similarly increased eosinophilia, IgE, tissue inflammation and MCM. Frontiers Media S.A. 2021-08-16 /pmc/articles/PMC8415780/ /pubmed/34485171 http://dx.doi.org/10.3389/fcimb.2021.683194 Text en Copyright © 2021 Daines, Pereira, Cunningham, Pryor, Besselsen, Liu, Luo and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Daines, Michael
Pereira, Rhea
Cunningham, Aubrey
Pryor, Barry
Besselsen, David G.
Liu, Yuchen
Luo, Qianwen
Chen, Yin
Novel Mouse Models of Fungal Asthma
title Novel Mouse Models of Fungal Asthma
title_full Novel Mouse Models of Fungal Asthma
title_fullStr Novel Mouse Models of Fungal Asthma
title_full_unstemmed Novel Mouse Models of Fungal Asthma
title_short Novel Mouse Models of Fungal Asthma
title_sort novel mouse models of fungal asthma
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415780/
https://www.ncbi.nlm.nih.gov/pubmed/34485171
http://dx.doi.org/10.3389/fcimb.2021.683194
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