Galactosaminogalactan activates the inflammasome to provide host protection

Inflammasomes are important sentinels of innate immune defence that are activated in response to diverse stimuli, including pathogen-associated molecular patterns (PAMPs). Activation of the inflammasome provides host defence against aspergillosis, which is a major health concern for patients who are...

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Detalles Bibliográficos
Autores: Briard, Benoit, Fontaine, Thierry, Samir, Parimal, Place, David E, Muszkieta, Laetitia, Malireddi, R K Subbarao, Karki, Rajendra, Christgen, Shelbi, Bomme, Perrine, Vogel, Peter, Beau, Rémi, Mellado, Emilia, Ibrahim-Granet, Oumaima, Henrissat, Bernard, Kalathur, Ravi C, Robinson, Cam, Latgé, Jean-Paul, Kanneganti, Thirumala-Devi
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/25973
Acceso en línea:https://hdl.handle.net/20.500.12105/25973
Access Level:acceso abierto
Palabra clave:Animals
Aspergillosis
Aspergillus fumigatus
Biofilms
Colitis
Dextran Sulfate
Female
Fungal Proteins
Gene Deletion
Immunity, Innate
Inflammasomes
Male
Mice
NLR Family, Pyrin Domain-Containing 3 Protein
Pathogen-Associated Molecular Pattern Molecules
Polysaccharides
Protein Biosynthesis
Ribosomal Proteins
Ribosomes
Descripción
Sumario:Inflammasomes are important sentinels of innate immune defence that are activated in response to diverse stimuli, including pathogen-associated molecular patterns (PAMPs). Activation of the inflammasome provides host defence against aspergillosis, which is a major health concern for patients who are immunocompromised. However, the Aspergillus fumigatus PAMPs that are responsible for inflammasome activation are not known. Here we show that the polysaccharide galactosaminogalactan (GAG) of A. fumigatus is a PAMP that activates the NLRP3 inflammasome. The binding of GAG to ribosomal proteins inhibited cellular translation machinery, and thus activated the NLRP3 inflammasome. The galactosamine moiety bound to ribosomal proteins and blocked cellular translation, which triggered activation of the NLRP3 inflammasome. In mice, a GAG-deficient Aspergillus mutant (Δgt4c) did not elicit protective activation of the inflammasome, and this strain exhibited enhanced virulence. Moreover, administration of GAG protected mice from colitis induced by dextran sulfate sodium in an inflammasome-dependent manner. Thus, ribosomes connect the sensing of this fungal PAMP to the activation of an innate immune response.

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