Por favor, use este identificador para citar o enlazar este ítem:
https://www.arca.fiocruz.br/handle/icict/34169
Tipo
ArtículoDerechos de autor
Acceso abierto
Objetivos de Desarrollo Sostenible
03 Saúde e Bem-EstarColecciones
Metadatos
Mostrar el registro completo del ítem
CRYPTOCOCCUS NEOFORMANS GLUCURONOXYLOMANNAN AND STERYLGLUCOSIDE ARE REQUIRED FOR HOST PROTECTION IN AN ANIMAL VACCINATION MODEL
Extracellular Vesicles
Mycoses
fungal infection
Glycolipids
Polysaccharides
Vaccines
Meningitis, Cryptococcal
Cápsulas
Vesículas Extracelulares
Micoses
Glicolipídeos
Polissacarídeos
Vacinas
Meningite Criptocócica
Autor
Afiliación
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Rio de Janeiro, RJ, Brasil. / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil. / Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA. / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA. / Chemical and Biomolecular Engineering Department. Ohio University. Athens, Ohio, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA. / Department of Medicine. Division of Infectious Diseases. Stony Brook University. Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA. / Department of Medicine. Division of Infectious Diseases. Stony Brook University. Stony Brook, New York, USA. / Veterans Administration Medical Center. Northport, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA. / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA. / Chemical and Biomolecular Engineering Department. Ohio University. Athens, Ohio, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA. / Department of Medicine. Division of Infectious Diseases. Stony Brook University. Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, New York, USA. / Department of Medicine. Division of Infectious Diseases. Stony Brook University. Stony Brook, New York, USA. / Veterans Administration Medical Center. Northport, New York, USA.
Resumen en ingles
Cryptococcus neoformans is an encapsulated fungal pathogen that causes meningoencephalitis. There are no prophylactic tools for cryptococcosis. Previously, our group showed that a C. neoformans mutant lacking the gene encoding sterylglucosidase (Δsgl1) induced protection in both immunocompetent and immunocompromised murine models of cryptococcosis. Since sterylglucosidase catalyzes degradation of sterylglucosides (SGs), accumulation of this glycolipid could be responsible for protective immunity. In this study, we analyzed whether the activity of SGs is sufficient for the protective effect induced by the Δsgl1 strain. We observed that the accumulation of SGs impacted several properties of the main polysaccharide that composes the fungal capsule, glucuronoxylomannan (GXM). We therefore used genetic manipulation to delete the SGL1 gene in the acapsular mutant Δcap59 to generate a double mutant (strain Δcap59/Δsgl1) that was shown to be nonpathogenic and cleared from the lung of mice within 7 days post-intranasal infection. The inflammatory immune response triggered by the Δcap59/Δsgl1 mutant in the lung differed from the response seen with the other strains. The double mutant did not induce protection in a vaccination model, suggesting that SG-related protection requires the main capsular polysaccharide. Finally, GXM-containing extracellular vesicles (EVs) enriched in SGs delayed the acute lethality of Galleria mellonella against C. neoformans infection. These studies highlighted a key role for GXM and SGs in inducing protection against a secondary cryptococcal infection, and, since EVs notoriously contain GXM, these results suggest the potential use of Δsgl1 EVs as a vaccination strategy for cryptococcosis. Important information: The number of deaths from cryptococcal meningitis is around 180,000 per year. The disease is the second leading cause of mortality among individuals with AIDS. Antifungal treatment is costly and associated with adverse effects and resistance, evidencing the urgency of development of both therapeutic and prophylactic tools. Here we demonstrate the key roles of polysaccharide- and glycolipid-containing structures in a vaccination model to prevent cryptococcosis.
Palabras clave en ingles
CapsulesExtracellular Vesicles
Mycoses
fungal infection
Glycolipids
Polysaccharides
Vaccines
Meningitis, Cryptococcal
DeCS
Cryptococcus neoformansCápsulas
Vesículas Extracelulares
Micoses
Glicolipídeos
Polissacarídeos
Vacinas
Meningite Criptocócica
Compartir