Open AccessGalactosaminogalactan activates the inflammasome to provide host protection
Author(s) -
Benoit Briard,
Thierry Fontaine,
Parimal Samir,
David E. Place,
Laetitia Muszkieta,
R. K. Subbarao Malireddi,
Rajendra Karki,
Shelbi Christgen,
Perrine Bomme,
Peter Vogel,
Rémi Beau,
Emilia Mellado,
Oumaïma Ibrahim-Granet,
Bernard Henrissat,
Ravi C. Kalathur,
Camenzind Robinson,
JeanPaul Latgé,
ThirumalaDevi Kanneganti
Publication year - 2020
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-020-2996-z
Subject(s) - inflammasome , innate immune system , aspergillus fumigatus , microbiology and biotechnology , aim2 , biology , immune system , caspase 1 , chemistry , immunology , inflammation
Inflammasomes are important sentinels of innate immune defence that are activated in response to diverse stimuli, including pathogen-associated molecular patterns (PAMPs) 1 . Activation of the inflammasome provides host defence against aspergillosis 2,3 , 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.