Pre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.3389/fcimb.2022.898619 http://hdl.handle.net/1843/60294 https://orcid.org/0000-0003-4720-6746 |
Resumo: | Aspergillus fumigatus is a ubiquitous and saprophytic filamentous fungus and the main etiologic agent of aspergillosis. Infections caused by A. fumigatus culminate in a strong inflammatory response that can evolve into respiratory failure and may be lethal in immunocompromised individuals. In the last decades, it has been demonstrated that extracellular vesicles (EVs) elicit a notable biological response in immune cells. EVs carry a variety of biomolecules, therefore are considered potential antigen delivery vehicles. The role of EVs as a strategy for modulating an effective response against infections caused by A. fumigatus remains unexplored. Here we investigate the use of EVs derived from A. fumigatus as an immunization tool to induce a more robust immune response to A. fumigatus pulmonary infection. In order to investigate that, male C57BL/6 mice were immunized with two doses of EVs and infected with A. fumigatus. Pre-exposure of mice to EVs was able to induce the production of specific IgG serum for fungal antigens. Besides that, the immunization with EVs reduced the neutrophilic infiltrate into the alveoli, as well as the extravasation of total proteins and the production of proinflammatory mediators IL-1b, IL-6, and CXCL-1. In addition, immunization prevented extensive lung tissue damage and also improved phagocytosis and fungus clearance. Noteworthy, immunization with EVs, associated with subclinical doses of Amphotericin B (AmB) treatment, rescued 50% of mice infected with A. fumigatus from lethal fungal pneumonia. Therefore, the present study shows a new role for A. fumigatus EVs as host inflammatory response modulators, suggesting their use as immunizing agents. |
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2023-10-30T21:36:33Z2023-10-30T21:36:33Z2022-06-0112113https://doi.org/10.3389/fcimb.2022.89861922352988http://hdl.handle.net/1843/60294https://orcid.org/0000-0003-4720-6746Aspergillus fumigatus is a ubiquitous and saprophytic filamentous fungus and the main etiologic agent of aspergillosis. Infections caused by A. fumigatus culminate in a strong inflammatory response that can evolve into respiratory failure and may be lethal in immunocompromised individuals. In the last decades, it has been demonstrated that extracellular vesicles (EVs) elicit a notable biological response in immune cells. EVs carry a variety of biomolecules, therefore are considered potential antigen delivery vehicles. The role of EVs as a strategy for modulating an effective response against infections caused by A. fumigatus remains unexplored. Here we investigate the use of EVs derived from A. fumigatus as an immunization tool to induce a more robust immune response to A. fumigatus pulmonary infection. In order to investigate that, male C57BL/6 mice were immunized with two doses of EVs and infected with A. fumigatus. Pre-exposure of mice to EVs was able to induce the production of specific IgG serum for fungal antigens. Besides that, the immunization with EVs reduced the neutrophilic infiltrate into the alveoli, as well as the extravasation of total proteins and the production of proinflammatory mediators IL-1b, IL-6, and CXCL-1. In addition, immunization prevented extensive lung tissue damage and also improved phagocytosis and fungus clearance. Noteworthy, immunization with EVs, associated with subclinical doses of Amphotericin B (AmB) treatment, rescued 50% of mice infected with A. fumigatus from lethal fungal pneumonia. Therefore, the present study shows a new role for A. fumigatus EVs as host inflammatory response modulators, suggesting their use as immunizing agents.porUniversidade Federal de Minas GeraisUFMGBrasilICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIAICB - DEPARTAMENTO DE FARMACOLOGIAICB - DEPARTAMENTO DE MORFOLOGIAFrontiers in Cellular and Infection MicrobiologyVesículas extracelularesAspergillus fumigatusImunizaçãoInterações hospedeiro-patógenoExtracellular vesiclesFilamentous fungusAspergillus fumigatusImmunizationHost-pathogen interactionsPre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.frontiersin.org/articles/10.3389/fcimb.2022.898619/fullJéssica Amanda Marques SouzaIsabella Luísa da Silva GurgelNathália Luísa Sousa de Oliveira MalaccoFlávia Rayssa Braga MartinsCelso Martins Queiroz JuniorMauro Martins TeixeiraFrederico Marianetti Sorianiapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/60294/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALPre-exposure with extracellular vesicles from aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis.pdfPre-exposure with extracellular vesicles from aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis.pdfapplication/pdf2812009https://repositorio.ufmg.br/bitstream/1843/60294/2/Pre-exposure%20with%20extracellular%20vesicles%20from%20aspergillus%20fumigatus%20attenuates%20inflammatory%20response%20and%20enhances%20fungal%20clearance%20in%20a%20murine%20model%20pulmonary%20aspergillosis.pdf0bcb47dbf0a4f63f5ddf5c723b4662f7MD521843/602942023-10-30 18:36:34.071oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-10-30T21:36:34Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Pre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis |
title |
Pre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis |
spellingShingle |
Pre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis Jéssica Amanda Marques Souza Extracellular vesicles Filamentous fungus Aspergillus fumigatus Immunization Host-pathogen interactions Vesículas extracelulares Aspergillus fumigatus Imunização Interações hospedeiro-patógeno |
title_short |
Pre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis |
title_full |
Pre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis |
title_fullStr |
Pre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis |
title_full_unstemmed |
Pre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis |
title_sort |
Pre-exposure with extracellular vesicles from Aspergillus fumigatus attenuates inflammatory response and enhances fungal clearance in a murine model pulmonary aspergillosis |
author |
Jéssica Amanda Marques Souza |
author_facet |
Jéssica Amanda Marques Souza Isabella Luísa da Silva Gurgel Nathália Luísa Sousa de Oliveira Malacco Flávia Rayssa Braga Martins Celso Martins Queiroz Junior Mauro Martins Teixeira Frederico Marianetti Soriani |
author_role |
author |
author2 |
Isabella Luísa da Silva Gurgel Nathália Luísa Sousa de Oliveira Malacco Flávia Rayssa Braga Martins Celso Martins Queiroz Junior Mauro Martins Teixeira Frederico Marianetti Soriani |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Jéssica Amanda Marques Souza Isabella Luísa da Silva Gurgel Nathália Luísa Sousa de Oliveira Malacco Flávia Rayssa Braga Martins Celso Martins Queiroz Junior Mauro Martins Teixeira Frederico Marianetti Soriani |
dc.subject.por.fl_str_mv |
Extracellular vesicles Filamentous fungus Aspergillus fumigatus Immunization Host-pathogen interactions |
topic |
Extracellular vesicles Filamentous fungus Aspergillus fumigatus Immunization Host-pathogen interactions Vesículas extracelulares Aspergillus fumigatus Imunização Interações hospedeiro-patógeno |
dc.subject.other.pt_BR.fl_str_mv |
Vesículas extracelulares Aspergillus fumigatus Imunização Interações hospedeiro-patógeno |
description |
Aspergillus fumigatus is a ubiquitous and saprophytic filamentous fungus and the main etiologic agent of aspergillosis. Infections caused by A. fumigatus culminate in a strong inflammatory response that can evolve into respiratory failure and may be lethal in immunocompromised individuals. In the last decades, it has been demonstrated that extracellular vesicles (EVs) elicit a notable biological response in immune cells. EVs carry a variety of biomolecules, therefore are considered potential antigen delivery vehicles. The role of EVs as a strategy for modulating an effective response against infections caused by A. fumigatus remains unexplored. Here we investigate the use of EVs derived from A. fumigatus as an immunization tool to induce a more robust immune response to A. fumigatus pulmonary infection. In order to investigate that, male C57BL/6 mice were immunized with two doses of EVs and infected with A. fumigatus. Pre-exposure of mice to EVs was able to induce the production of specific IgG serum for fungal antigens. Besides that, the immunization with EVs reduced the neutrophilic infiltrate into the alveoli, as well as the extravasation of total proteins and the production of proinflammatory mediators IL-1b, IL-6, and CXCL-1. In addition, immunization prevented extensive lung tissue damage and also improved phagocytosis and fungus clearance. Noteworthy, immunization with EVs, associated with subclinical doses of Amphotericin B (AmB) treatment, rescued 50% of mice infected with A. fumigatus from lethal fungal pneumonia. Therefore, the present study shows a new role for A. fumigatus EVs as host inflammatory response modulators, suggesting their use as immunizing agents. |
publishDate |
2022 |
dc.date.issued.fl_str_mv |
2022-06-01 |
dc.date.accessioned.fl_str_mv |
2023-10-30T21:36:33Z |
dc.date.available.fl_str_mv |
2023-10-30T21:36:33Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/60294 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.3389/fcimb.2022.898619 |
dc.identifier.issn.pt_BR.fl_str_mv |
22352988 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0003-4720-6746 |
url |
https://doi.org/10.3389/fcimb.2022.898619 http://hdl.handle.net/1843/60294 https://orcid.org/0000-0003-4720-6746 |
identifier_str_mv |
22352988 |
dc.language.iso.fl_str_mv |
por |
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por |
dc.relation.ispartof.pt_BR.fl_str_mv |
Frontiers in Cellular and Infection Microbiology |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
dc.publisher.initials.fl_str_mv |
UFMG |
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Brasil |
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ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA ICB - DEPARTAMENTO DE FARMACOLOGIA ICB - DEPARTAMENTO DE MORFOLOGIA |
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Universidade Federal de Minas Gerais |
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