Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulans
IntroductionInvasive aspergillosis (IA) is the most prevalent infectious complication in patients with chronic granulomatous disease (CGD). Yet, understanding of fungal pathogenesis in the CGD host remains limited, particularly with regards to A. nidulans infection.MethodsWe have used a murine model...
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1241770/full |
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| author | Jill King Jill King Jill King Ivy M. Dambuza Ivy M. Dambuza Delyth M. Reid Raif Yuecel Raif Yuecel Gordon D. Brown Gordon D. Brown Adilia Warris Adilia Warris |
| author_facet | Jill King Jill King Jill King Ivy M. Dambuza Ivy M. Dambuza Delyth M. Reid Raif Yuecel Raif Yuecel Gordon D. Brown Gordon D. Brown Adilia Warris Adilia Warris |
| author_sort | Jill King |
| collection | DOAJ |
| description | IntroductionInvasive aspergillosis (IA) is the most prevalent infectious complication in patients with chronic granulomatous disease (CGD). Yet, understanding of fungal pathogenesis in the CGD host remains limited, particularly with regards to A. nidulans infection.MethodsWe have used a murine model of X-linked CGD to investigate how the pathogenesis of IA varies between A. fumigatus and A. nidulans, comparing infection in both X-linked CGD (gp91-/-) mice and their parent C57BL/6 (WT) mice. A 14-colour flow cytometry panel was used to assess the cell dynamics over the course of infection, with parallel assessment of pulmonary cytokine production and lung histology.ResultsWe observed a lack of association between pulmonary pathology and infection outcome in gp91-/- mice, with no significant mortality in A. nidulans infected mice. An overwhelming and persistent neutrophil recruitment and IL-1 release in gp91-/- mice following both A. fumigatus and A. nidulans infection was observed, with divergent macrophage, dendritic cell and eosinophil responses and distinct cytokine profiles between the two infections.ConclusionWe have provided an in-depth characterisation of the immune response to pulmonary aspergillosis in an X-linked CGD murine model. This provides the first description of distinct pulmonary inflammatory environments in A. fumigatus and A. nidulans infection in X-linked CGD and identifies several new avenues for further research. |
| first_indexed | 2024-03-12T11:25:53Z |
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| id | doaj.art-20e085bc85d14db58d3f183e76b1ad6f |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-03-12T11:25:53Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-20e085bc85d14db58d3f183e76b1ad6f2023-09-01T08:08:40ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-09-011310.3389/fcimb.2023.12417701241770Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulansJill King0Jill King1Jill King2Ivy M. Dambuza3Ivy M. Dambuza4Delyth M. Reid5Raif Yuecel6Raif Yuecel7Gordon D. Brown8Gordon D. Brown9Adilia Warris10Adilia Warris11Medical Research Council (MRC) Centre for Medical Mycology, University of Exeter, Exeter, United KingdomMRC Centre for Medical Mycology Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United KingdomDepartment of General Paediatrics, Royal Aberdeen Children’s Hospital, Aberdeen, United KingdomMedical Research Council (MRC) Centre for Medical Mycology, University of Exeter, Exeter, United KingdomMRC Centre for Medical Mycology Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United KingdomMRC Centre for Medical Mycology Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United KingdomExeter Centre for Cytometrics, University of Exeter, Exeter, United KingdomIain Fraser Cytometry Centre, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United KingdomMedical Research Council (MRC) Centre for Medical Mycology, University of Exeter, Exeter, United KingdomMRC Centre for Medical Mycology Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United KingdomMedical Research Council (MRC) Centre for Medical Mycology, University of Exeter, Exeter, United KingdomMRC Centre for Medical Mycology Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United KingdomIntroductionInvasive aspergillosis (IA) is the most prevalent infectious complication in patients with chronic granulomatous disease (CGD). Yet, understanding of fungal pathogenesis in the CGD host remains limited, particularly with regards to A. nidulans infection.MethodsWe have used a murine model of X-linked CGD to investigate how the pathogenesis of IA varies between A. fumigatus and A. nidulans, comparing infection in both X-linked CGD (gp91-/-) mice and their parent C57BL/6 (WT) mice. A 14-colour flow cytometry panel was used to assess the cell dynamics over the course of infection, with parallel assessment of pulmonary cytokine production and lung histology.ResultsWe observed a lack of association between pulmonary pathology and infection outcome in gp91-/- mice, with no significant mortality in A. nidulans infected mice. An overwhelming and persistent neutrophil recruitment and IL-1 release in gp91-/- mice following both A. fumigatus and A. nidulans infection was observed, with divergent macrophage, dendritic cell and eosinophil responses and distinct cytokine profiles between the two infections.ConclusionWe have provided an in-depth characterisation of the immune response to pulmonary aspergillosis in an X-linked CGD murine model. This provides the first description of distinct pulmonary inflammatory environments in A. fumigatus and A. nidulans infection in X-linked CGD and identifies several new avenues for further research.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1241770/fullchronic granulomatous diseaseAspergillus fumigatusAspergillus nidulansmurineinfectioninflammation |
| spellingShingle | Jill King Jill King Jill King Ivy M. Dambuza Ivy M. Dambuza Delyth M. Reid Raif Yuecel Raif Yuecel Gordon D. Brown Gordon D. Brown Adilia Warris Adilia Warris Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulans Frontiers in Cellular and Infection Microbiology chronic granulomatous disease Aspergillus fumigatus Aspergillus nidulans murine infection inflammation |
| title | Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulans |
| title_full | Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulans |
| title_fullStr | Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulans |
| title_full_unstemmed | Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulans |
| title_short | Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulans |
| title_sort | detailed characterisation of invasive aspergillosis in a murine model of x linked chronic granulomatous disease shows new insights in infections caused by aspergillus fumigatus versus aspergillus nidulans |
| topic | chronic granulomatous disease Aspergillus fumigatus Aspergillus nidulans murine infection inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1241770/full |
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