Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

  • Cell Rep Med. 2023 Jan 17;4(1):100899. doi: 10.1016/j.xcrm.2022.100899.
Natalia Muñoz-Wolf  1 ,  Ross W Ward  2 ,  Claire H Hearnden  2 ,  Fiona A Sharp  2 ,  Joan Geoghegan  3 ,  Katie O'Grady  2 ,  Craig P McEntee  2 ,  Katharine A Shanahan  4 ,  Coralie Guy  4 ,  Andrew G Bowie  4 ,  Matthew Campbell  5 ,  Carla B Roces  6 ,  Giulia Anderluzzi  6 ,  Cameron Webb  6 ,  Yvonne Perrie  6 ,  Emma Creagh  4 ,  Ed C Lavelle  7
Affiliations
  • 1. Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 D02 R590, Ireland; Translational & Respiratory Immunology Lab, Department of Clinical Medicine, School of Medicine, Trinity Biomedical Sciences Institute, Dublin D02 R590, Ireland; Clinical Medicine Tallaght University Hospital, Dublin D24 NR04, Ireland.
  • 2. Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 D02 R590, Ireland.
  • 3. Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland; Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
  • 4. School of Biochemistry and Immunology, Trinity Biomedical Science Institute (TBSI), Trinity College Dublin, Dublin D02 R590, Ireland.
  • 5. Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
  • 6. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK.
  • 7. Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 D02 R590, Ireland; Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN) & Advanced Materials Bio-Engineering Research Centre (AMBER), Trinity College Dublin, Dublin D02 PN40, Ireland. Electronic address: [email protected].
PMID: 36652908 DOI: 10.1016/j.xcrm.2022.100899
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.

Keywords
CD4; CD8+; CTL; Caspase-1; Caspase-11; GSDMD; IL-1; PLGA; T cells; Th1; adjuvant; cell-mediated immunity; non-canonical inflammasome; polymeric nanoparticles; vaccine.
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