| First Author | Muñoz-Wolf N | Year | 2023 |
| Journal | Cell Rep Med | Volume | 4 |
| Issue | 1 | Pages | 100899 |
| PubMed ID | 36652908 | Mgi Jnum | J:347650 |
| Mgi Id | MGI:7618859 | Doi | 10.1016/j.xcrm.2022.100899 |
| Citation | Munoz-Wolf N, et al. (2023) Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles. Cell Rep Med 4(1):100899 |
| abstractText | 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. |
