Galactosaminogalactan activates the inflammasome to provide host protection

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, Oumaima Ibrahim-Granet, Bernard Henrissat, Ravi C. Kalathur, Cam Robinson, Jean Paul Latgé, Thirumala Devi Kanneganti

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

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 aspergillosis2,3, 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.

Original languageEnglish (US)
Pages (from-to)688-692
Number of pages5
JournalNature
Volume588
Issue number7839
DOIs
StatePublished - Dec 24 2020
Externally publishedYes

ASJC Scopus subject areas

  • General

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