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oai:repisalud.isciii.es:20.500.12105/259732025-12-18T12:52:34Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Briard, Benoit author Fontaine, Thierry author Samir, Parimal author Place, David E author Muszkieta, Laetitia author Malireddi, R K Subbarao author Karki, Rajendra author Christgen, Shelbi author Bomme, Perrine author Vogel, Peter author Beau, Rémi author Mellado, Emilia author Ibrahim-Granet, Oumaima author Henrissat, Bernard author Kalathur, Ravi C author Robinson, Cam author Latgé, Jean-Paul author Kanneganti, Thirumala-Devi author 2020-12 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. Briard B, Fontaine T, Samir P, Place DE, Muszkieta L, Malireddi RKS, Karki R, Christgen S, Bomme P, Vogel P, Beau R, Mellado E, Ibrahim-Granet O, Henrissat B, Kalathur RC, Robinson C, Latgé JP, Kanneganti TD. Galactosaminogalactan activates the inflammasome to provide host protection. Nature. 2020 Dec;588(7839):688-692. 0028-0836 https://pmc.ncbi.nlm.nih.gov/articles/PMC8086055/ https://hdl.handle.net/20.500.12105/25973 33268895 10.1038/s41586-020-2996-z 1476-4687 Nature Galactosaminogalactan activates the inflammasome to provide host protection