Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

Natalia Muñoz-Wolf, Ross W Ward, Claire H Hearnden, Fiona A Sharp, Joan Geoghegan, Katie O'Grady, Craig P McEntee, Katharine A Shanahan, Coralie Guy, Andrew G Bowie, Matthew Campbell, Carla B Roces, Giulia Anderluzzi, Cameron Webb, Yvonne Perrie, Emma Creagh, Ed C Lavelle*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

The non-canonical inflammasome sensor caspase-11 and gasdermin D (GSDMD) drive inflammation and pyroptosis, a type of immunogenic cell death that favors cell-mediated immunity (CMI) in cancer, infection, and autoimmunity. Here we show that caspase-11 and GSDMD are required for CD8 + and Th1 responses induced by nanoparticulate vaccine adjuvants. We demonstrate that nanoparticle-induced reactive oxygen species (ROS) are size dependent and essential for CMI, and we identify 50- to 60-nm nanoparticles as optimal inducers of ROS, GSDMD activation, and Th1 and CD8+ responses. We reveal a division of labor for IL-1 and IL-18, where IL-1 supports Th1 and IL-18 promotes CD8+ responses. Exploiting size as a key attribute, we demonstrate that biodegradable poly-lactic co-glycolic acid nanoparticles are potent CMI-inducing adjuvants. Our work implicates ROS and the non-canonical inflammasome in the mode of action of polymeric nanoparticulate adjuvants and establishes adjuvant size as a key design principle for vaccines against cancer and intracellular pathogens.

Original languageEnglish
Article number100899
Number of pages21
JournalCell Reports Medicine
Volume4
Issue number1
DOIs
Publication statusPublished - 17 Jan 2023

Bibliographical note

Copyright © 2022 The Author(s). Published by Elsevier Inc.

Keywords

  • Inflammasomes/metabolism
  • Interleukin-18/metabolism
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Reactive Oxygen Species/metabolism
  • Phosphate-Binding Proteins/metabolism
  • Caspases/metabolism
  • Interleukin-1/metabolism
  • Nanoparticles

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