Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Interactions

ABSTRACT Aspergillus fumigatus is an opportunistic fungal pathogen that can cause life-threatening invasive lung infections in immunodeficient patients. The cellular and molecular processes of infection during onset, establishment, and progression of A. fumigatus infections are highly complex and de...

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Autores principales:	Jorge Amich, Zeinab Mokhtari, Marlene Strobel, Elena Vialetto, Dalia Sheta, Yidong Yu, Julia Hartweg, Natarajaswamy Kalleda, Katja J. Jarick, Christian Brede, Ana-Laura Jordán-Garrote, Sina Thusek, Katharina Schmiedgen, Berkan Arslan, Jürgen Pinnecker, Christopher R. Thornton, Matthias Gunzer, Sven Krappmann, Hermann Einsele, Katrin G. Heinze, Andreas Beilhack
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Aspergillus fumigatus invasive aspergillosis host-pathogen interactions lung infection lung immunity microscopy/imaging Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/82d55ec447f5437f9319f8415e6f5b16
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spelling	oai:doaj.org-article:82d55ec447f5437f9319f8415e6f5b162021-11-15T15:56:58ZThree-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Interactions10.1128/mBio.02752-192150-7511https://doaj.org/article/82d55ec447f5437f9319f8415e6f5b162020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02752-19https://doaj.org/toc/2150-7511ABSTRACT Aspergillus fumigatus is an opportunistic fungal pathogen that can cause life-threatening invasive lung infections in immunodeficient patients. The cellular and molecular processes of infection during onset, establishment, and progression of A. fumigatus infections are highly complex and depend on both fungal attributes and the immune status of the host. Therefore, preclinical animal models are of paramount importance to investigate and gain better insight into the infection process. Yet, despite their extensive use, commonly employed murine models of invasive pulmonary aspergillosis are not well understood due to analytical limitations. Here, we present quantitative light sheet fluorescence microscopy (LSFM) to describe fungal growth and the local immune response in whole lungs at cellular resolution within its anatomical context. We analyzed three very common murine models of pulmonary aspergillosis based on immunosuppression with corticosteroids, chemotherapy-induced leukopenia, or myeloablative irradiation. LSFM uncovered distinct architectures of fungal growth and degrees of tissue invasion in each model. Furthermore, LSFM revealed the spatial distribution, interaction, and activation of two key immune cell populations in antifungal defense: alveolar macrophages and polymorphonuclear neutrophils. Interestingly, the patterns of fungal growth correlated with the detected effects of the immunosuppressive regimens on the local immune cell populations. Moreover, LSFM demonstrates that the commonly used intranasal route of spore administration did not result in complete intra-alveolar deposition, as about 80% of fungal growth occurred outside the alveolar space. Hence, characterization by LSFM is more rigorous than by previously used methods employing murine models of invasive pulmonary aspergillosis and pinpoints their strengths and limitations. IMPORTANCE The use of animal models of infection is essential to advance our understanding of the complex host-pathogen interactions that take place during Aspergillus fumigatus lung infections. As in the case of humans, mice need to suffer an immune imbalance in order to become susceptible to invasive pulmonary aspergillosis (IPA), the most serious infection caused by A. fumigatus. There are several immunosuppressive regimens that are routinely used to investigate fungal growth and/or immune responses in murine models of invasive pulmonary aspergillosis. However, the precise consequences of the use of each immunosuppressive model for the local immune populations and for fungal growth are not completely understood. Here, to pin down the scenarios involving commonly used IPA models, we employed light sheet fluorescence microscopy (LSFM) to analyze whole lungs at cellular resolution. Our results will be valuable to optimize and refine animal models to maximize their use in future research.Jorge AmichZeinab MokhtariMarlene StrobelElena VialettoDalia ShetaYidong YuJulia HartwegNatarajaswamy KalledaKatja J. JarickChristian BredeAna-Laura Jordán-GarroteSina ThusekKatharina SchmiedgenBerkan ArslanJürgen PinneckerChristopher R. ThorntonMatthias GunzerSven KrappmannHermann EinseleKatrin G. HeinzeAndreas BeilhackAmerican Society for MicrobiologyarticleAspergillus fumigatusinvasive aspergillosishost-pathogen interactionslung infectionlung immunitymicroscopy/imagingMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus invasive aspergillosis host-pathogen interactions lung infection lung immunity microscopy/imaging Microbiology QR1-502
spellingShingle	Aspergillus fumigatus invasive aspergillosis host-pathogen interactions lung infection lung immunity microscopy/imaging Microbiology QR1-502 Jorge Amich Zeinab Mokhtari Marlene Strobel Elena Vialetto Dalia Sheta Yidong Yu Julia Hartweg Natarajaswamy Kalleda Katja J. Jarick Christian Brede Ana-Laura Jordán-Garrote Sina Thusek Katharina Schmiedgen Berkan Arslan Jürgen Pinnecker Christopher R. Thornton Matthias Gunzer Sven Krappmann Hermann Einsele Katrin G. Heinze Andreas Beilhack Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Interactions
description	ABSTRACT Aspergillus fumigatus is an opportunistic fungal pathogen that can cause life-threatening invasive lung infections in immunodeficient patients. The cellular and molecular processes of infection during onset, establishment, and progression of A. fumigatus infections are highly complex and depend on both fungal attributes and the immune status of the host. Therefore, preclinical animal models are of paramount importance to investigate and gain better insight into the infection process. Yet, despite their extensive use, commonly employed murine models of invasive pulmonary aspergillosis are not well understood due to analytical limitations. Here, we present quantitative light sheet fluorescence microscopy (LSFM) to describe fungal growth and the local immune response in whole lungs at cellular resolution within its anatomical context. We analyzed three very common murine models of pulmonary aspergillosis based on immunosuppression with corticosteroids, chemotherapy-induced leukopenia, or myeloablative irradiation. LSFM uncovered distinct architectures of fungal growth and degrees of tissue invasion in each model. Furthermore, LSFM revealed the spatial distribution, interaction, and activation of two key immune cell populations in antifungal defense: alveolar macrophages and polymorphonuclear neutrophils. Interestingly, the patterns of fungal growth correlated with the detected effects of the immunosuppressive regimens on the local immune cell populations. Moreover, LSFM demonstrates that the commonly used intranasal route of spore administration did not result in complete intra-alveolar deposition, as about 80% of fungal growth occurred outside the alveolar space. Hence, characterization by LSFM is more rigorous than by previously used methods employing murine models of invasive pulmonary aspergillosis and pinpoints their strengths and limitations. IMPORTANCE The use of animal models of infection is essential to advance our understanding of the complex host-pathogen interactions that take place during Aspergillus fumigatus lung infections. As in the case of humans, mice need to suffer an immune imbalance in order to become susceptible to invasive pulmonary aspergillosis (IPA), the most serious infection caused by A. fumigatus. There are several immunosuppressive regimens that are routinely used to investigate fungal growth and/or immune responses in murine models of invasive pulmonary aspergillosis. However, the precise consequences of the use of each immunosuppressive model for the local immune populations and for fungal growth are not completely understood. Here, to pin down the scenarios involving commonly used IPA models, we employed light sheet fluorescence microscopy (LSFM) to analyze whole lungs at cellular resolution. Our results will be valuable to optimize and refine animal models to maximize their use in future research.
format	article
author	Jorge Amich Zeinab Mokhtari Marlene Strobel Elena Vialetto Dalia Sheta Yidong Yu Julia Hartweg Natarajaswamy Kalleda Katja J. Jarick Christian Brede Ana-Laura Jordán-Garrote Sina Thusek Katharina Schmiedgen Berkan Arslan Jürgen Pinnecker Christopher R. Thornton Matthias Gunzer Sven Krappmann Hermann Einsele Katrin G. Heinze Andreas Beilhack
author_facet	Jorge Amich Zeinab Mokhtari Marlene Strobel Elena Vialetto Dalia Sheta Yidong Yu Julia Hartweg Natarajaswamy Kalleda Katja J. Jarick Christian Brede Ana-Laura Jordán-Garrote Sina Thusek Katharina Schmiedgen Berkan Arslan Jürgen Pinnecker Christopher R. Thornton Matthias Gunzer Sven Krappmann Hermann Einsele Katrin G. Heinze Andreas Beilhack
author_sort	Jorge Amich
title	Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Interactions
title_short	Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Interactions
title_full	Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Interactions
title_fullStr	Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Interactions
title_full_unstemmed	Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Interactions
title_sort	three-dimensional light sheet fluorescence microscopy of lungs to dissect local host immune-<named-content content-type="genus-species">aspergillus fumigatus</named-content> interactions
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/82d55ec447f5437f9319f8415e6f5b16
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Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Interactions

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