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

doi:10.1016/j.xcrm.2022.100899

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

Microbiology and Infection

Research output: Contribution to journal › Article › peer-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 language	English
Article number	100899
Number of pages	21
Journal	Cell Reports Medicine
Volume	4
Issue number	1
DOIs	https://doi.org/10.1016/j.xcrm.2022.100899
Publication status	Published - 17 Jan 2023

Bibliographical note

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.xcrm.2022.100899Licence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

MunozWolfN2022NoncanFinal published version, 3.5 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

Cite this

Muñoz-Wolf, N., Ward, R. W., Hearnden, C. H., Sharp, F. A., Geoghegan, J., O'Grady, K., McEntee, C. P., Shanahan, K. A., Guy, C., Bowie, A. G., Campbell, M., Roces, C. B., Anderluzzi, G., Webb, C., Perrie, Y., Creagh, E., & Lavelle, E. C. (2023). Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles. Cell Reports Medicine, 4(1), Article 100899. https://doi.org/10.1016/j.xcrm.2022.100899

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title = "Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles",

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 = "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",

author = "Natalia Mu{\~n}oz-Wolf and Ward, {Ross W} and Hearnden, {Claire H} and Sharp, {Fiona A} and Joan Geoghegan and Katie O'Grady and McEntee, {Craig P} and Shanahan, {Katharine A} and Coralie Guy and Bowie, {Andrew G} and Matthew Campbell and Roces, {Carla B} and Giulia Anderluzzi and Cameron Webb and Yvonne Perrie and Emma Creagh and Lavelle, {Ed C}",

note = "Copyright {\textcopyright} 2022 The Author(s). Published by Elsevier Inc.",

year = "2023",

month = jan,

day = "17",

doi = "10.1016/j.xcrm.2022.100899",

language = "English",

volume = "4",

journal = "Cell Reports Medicine",

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Muñoz-Wolf, N, Ward, RW, Hearnden, CH, Sharp, FA, Geoghegan, J, O'Grady, K, McEntee, CP, Shanahan, KA, Guy, C, Bowie, AG, Campbell, M, Roces, CB, Anderluzzi, G, Webb, C, Perrie, Y, Creagh, E & Lavelle, EC 2023, 'Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles', Cell Reports Medicine, vol. 4, no. 1, 100899. https://doi.org/10.1016/j.xcrm.2022.100899

TY - JOUR

T1 - Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

AU - Muñoz-Wolf, Natalia

AU - Ward, Ross W

AU - Hearnden, Claire H

AU - Sharp, Fiona A

AU - Geoghegan, Joan

AU - O'Grady, Katie

AU - McEntee, Craig P

AU - Shanahan, Katharine A

AU - Guy, Coralie

AU - Bowie, Andrew G

AU - Campbell, Matthew

AU - Roces, Carla B

AU - Anderluzzi, Giulia

AU - Webb, Cameron

AU - Perrie, Yvonne

AU - Creagh, Emma

AU - Lavelle, Ed C

PY - 2023/1/17

Y1 - 2023/1/17

N2 - 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.

AB - 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.

KW - Inflammasomes/metabolism

KW - Interleukin-18/metabolism

KW - Intracellular Signaling Peptides and Proteins/metabolism

KW - Reactive Oxygen Species/metabolism

KW - Phosphate-Binding Proteins/metabolism

KW - Caspases/metabolism

KW - Interleukin-1/metabolism

KW - Nanoparticles

U2 - 10.1016/j.xcrm.2022.100899

DO - 10.1016/j.xcrm.2022.100899

M3 - Article

C2 - 36652908

SN - 2666-3791

VL - 4

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 1

M1 - 100899

ER -

Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

Abstract

Bibliographical note

Keywords

UN SDGs

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