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

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

5 Downloads (Pure)

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	22
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

Keywords

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

UN SDGs

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

Access to Document

10.1016/j.xcrm.2022.100899Licence: CC BY-NC-ND 4.0

Muñoz-Wolf-etal-CRM-2023-Non-canonical-inflammasome-activation-mediates-the-adjuvanticity-of-nanoparticlesFinal published version, 3.59 MBLicence: CC BY-NC-ND 4.0

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), [100899]. https://doi.org/10.1016/j.xcrm.2022.100899

@article{3c2dd66e36bc4afebecc98fd5fd2a425,

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

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.}",

year = "2023",

month = jan,

day = "17",

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

language = "English",

volume = "4",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "1",

}

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 - adjuvant

KW - Caspase-1

KW - Caspase-11

KW - CD4

KW - CD8+

KW - cell-mediated immunity

KW - CTL

KW - GSDMD

KW - IL-1

KW - non-canonical inflammasome

KW - PLGA

KW - polymeric nanoparticles

KW - T cells

KW - Th1

KW - vaccine

U2 - 10.1016/j.xcrm.2022.100899

DO - 10.1016/j.xcrm.2022.100899

M3 - Article

C2 - 36652908

AN - SCOPUS:85146285876

VL - 4

JO - Cell Reports Medicine

JF - Cell Reports Medicine

SN - 2666-3791

IS - 1

M1 - 100899

ER -

Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this