Pre-Exposure With Extracellular Vesicles From Aspergillus fumigatus Attenuates Inflammatory Response and Enhances Fungal Clearance in a Murine Model Pulmonary Aspergillosis.

Autor:	Souza JAM; Centro de Pesquisa e Desenvolvimento de Fármacos, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Gurgel ILDS; Centro de Pesquisa e Desenvolvimento de Fármacos, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Malacco NLSO; Centro de Pesquisa e Desenvolvimento de Fármacos, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; The Lopes Lab, Institute of Parasitology, McGill University, Montreal, QC, Canada., Martins FRB; Centro de Pesquisa e Desenvolvimento de Fármacos, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Queiroz-Junior CM; Centro de Pesquisa e Desenvolvimento de Fármacos, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Teixeira MM; Centro de Pesquisa e Desenvolvimento de Fármacos, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Soriani FM; Centro de Pesquisa e Desenvolvimento de Fármacos, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2022 Jun 01; Vol. 12, pp. 898619. Date of Electronic Publication: 2022 Jun 01 (Print Publication: 2022).
DOI:	10.3389/fcimb.2022.898619
Abstrakt:	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-1β, 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Souza, Gurgel, Malacco, Martins, Queiroz-Junior, Teixeira and Soriani.)
Databáze:	MEDLINE
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