Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation

Abstract Background In patients with chronic obstructive pulmonary disease (COPD), a sensitization to A. fumigatus has been related to a decline in lung function, but the role of fungal agents in the disease pathogenesis remains unclear. The main purpose of the present study was to investigate wheth...

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Main Authors: Alexandra Bouyssi, Alexis Trecourt, Tanguy Déméautis, Florence Persat, Olivier Glehen, Martine Wallon, Gilles Devouassoux, Abderrazzak Bentaher, Jean Menotti
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Respiratory Research
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Online Access:https://doi.org/10.1186/s12931-024-03092-7
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author Alexandra Bouyssi
Alexis Trecourt
Tanguy Déméautis
Florence Persat
Olivier Glehen
Martine Wallon
Gilles Devouassoux
Abderrazzak Bentaher
Jean Menotti
author_facet Alexandra Bouyssi
Alexis Trecourt
Tanguy Déméautis
Florence Persat
Olivier Glehen
Martine Wallon
Gilles Devouassoux
Abderrazzak Bentaher
Jean Menotti
author_sort Alexandra Bouyssi
collection DOAJ
description Abstract Background In patients with chronic obstructive pulmonary disease (COPD), a sensitization to A. fumigatus has been related to a decline in lung function, but the role of fungal agents in the disease pathogenesis remains unclear. The main purpose of the present study was to investigate whether cell inflammation could worsen after exposure to A. fumigatus spores in vitro and then, in mice, following chronic exposure to cigarette smoke mimicking COPD. Methods The inflammatory response to cigarette smoke alone or with A. fumigatus was investigated in cell culture models of murine macrophages and alveolar epithelial cells. In an animal model, mice were exposed daily to two cigarettes smoke over 14 weeks, and two intranasal instillations of 105 spores at weeks 7 and 14. Then, their lungs were recovered to perform inflammatory and histopathological analyses. Results In co-cultures of macrophages and epithelial cells treated with both cigarette smoke extracts (CSE) and A. fumigatus compared to CSE alone there were significant inductions in TNF-α (6.2-fold) and CXCL-2 (21.5-fold) gene expression, confirmed by significant increases in the corresponding protein secretion. In the murine model, histological analyses of the lung after chronic smoke exposure showed an increase in airspace enlargement. Moreover, a Bio-Plex approach on bronchoalveolar lavage of cigarette smoke and A. fumigatus-treated mice showed significant increases in multiple inflammatory proteins secreted in the lung. Conclusions There was a stronger inflammatory response after cigarette smoke exposure with A. fumigatus compared to cigarette smoke alone. These findings were correlated with histopathological changes in the mouse lung in vivo.
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spelling doaj-art-352cacfc2fb8406d9fd39b15935442532025-01-19T12:36:31ZengBMCRespiratory Research1465-993X2025-01-0126111110.1186/s12931-024-03092-7Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbationAlexandra Bouyssi0Alexis Trecourt1Tanguy Déméautis2Florence Persat3Olivier Glehen4Martine Wallon5Gilles Devouassoux6Abderrazzak Bentaher7Jean Menotti8UR3738 CICLY Team Inflammation and Immunity of the Respiratory Epithelium, Claude Bernard UniversityUR3738 CICLY Team Inflammation and Immunity of the Respiratory Epithelium, Claude Bernard UniversityUR3738 CICLY Team Inflammation and Immunity of the Respiratory Epithelium, Claude Bernard UniversityUR3738 CICLY Team Inflammation and Immunity of the Respiratory Epithelium, Claude Bernard UniversitySurgical Department, UR3738 CICLY, Claude Bernard University – Lyon 1, South Lyon Hospital, Hospices Civils de LyonDepartment of Medical Mycology and Parasitology, Institute of Infectious Agents, Croix-Rousse Hospital, Hospices Civils de LyonUR3738 CICLY Team Inflammation and Immunity of the Respiratory Epithelium, Claude Bernard UniversityUR3738 CICLY Team Inflammation and Immunity of the Respiratory Epithelium, Claude Bernard UniversityUR3738 CICLY Team Inflammation and Immunity of the Respiratory Epithelium, Claude Bernard UniversityAbstract Background In patients with chronic obstructive pulmonary disease (COPD), a sensitization to A. fumigatus has been related to a decline in lung function, but the role of fungal agents in the disease pathogenesis remains unclear. The main purpose of the present study was to investigate whether cell inflammation could worsen after exposure to A. fumigatus spores in vitro and then, in mice, following chronic exposure to cigarette smoke mimicking COPD. Methods The inflammatory response to cigarette smoke alone or with A. fumigatus was investigated in cell culture models of murine macrophages and alveolar epithelial cells. In an animal model, mice were exposed daily to two cigarettes smoke over 14 weeks, and two intranasal instillations of 105 spores at weeks 7 and 14. Then, their lungs were recovered to perform inflammatory and histopathological analyses. Results In co-cultures of macrophages and epithelial cells treated with both cigarette smoke extracts (CSE) and A. fumigatus compared to CSE alone there were significant inductions in TNF-α (6.2-fold) and CXCL-2 (21.5-fold) gene expression, confirmed by significant increases in the corresponding protein secretion. In the murine model, histological analyses of the lung after chronic smoke exposure showed an increase in airspace enlargement. Moreover, a Bio-Plex approach on bronchoalveolar lavage of cigarette smoke and A. fumigatus-treated mice showed significant increases in multiple inflammatory proteins secreted in the lung. Conclusions There was a stronger inflammatory response after cigarette smoke exposure with A. fumigatus compared to cigarette smoke alone. These findings were correlated with histopathological changes in the mouse lung in vivo.https://doi.org/10.1186/s12931-024-03092-7Chronic obstructive pulmonary diseaseCigarette smokeExacerbationAspergillus fumigatusInflammationMurine model
spellingShingle Alexandra Bouyssi
Alexis Trecourt
Tanguy Déméautis
Florence Persat
Olivier Glehen
Martine Wallon
Gilles Devouassoux
Abderrazzak Bentaher
Jean Menotti
Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation
Respiratory Research
Chronic obstructive pulmonary disease
Cigarette smoke
Exacerbation
Aspergillus fumigatus
Inflammation
Murine model
title Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation
title_full Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation
title_fullStr Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation
title_full_unstemmed Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation
title_short Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation
title_sort aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation
topic Chronic obstructive pulmonary disease
Cigarette smoke
Exacerbation
Aspergillus fumigatus
Inflammation
Murine model
url https://doi.org/10.1186/s12931-024-03092-7
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