{"doi":"10.1016/j.xcrm.2022.100899","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.","journal":"Cell Reports Medicine","year":2023,"id":326035,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1044439,"name":"Ross W. Ward","orcid":"0000-0001-5242-4022","position":1,"is_corresponding":false},{"id":1044883,"name":"Claire H. Hearnden","orcid":null,"position":2,"is_corresponding":false},{"id":1044884,"name":"Fiona A. Sharp","orcid":null,"position":3,"is_corresponding":false},{"id":1044440,"name":"Joan A. Geoghegan","orcid":"0000-0002-3788-0668","position":4,"is_corresponding":false},{"id":1044885,"name":"Katie O’Grady","orcid":null,"position":5,"is_corresponding":false},{"id":1044441,"name":"Craig P. McEntee","orcid":"0000-0002-4762-7607","position":6,"is_corresponding":false},{"id":1044886,"name":"Katharine A. Shanahan","orcid":null,"position":7,"is_corresponding":false},{"id":1044887,"name":"Coralie Guy","orcid":null,"position":8,"is_corresponding":false},{"id":612073,"name":"Andrew Bowie","orcid":"0000-0001-5316-4373","position":9,"is_corresponding":false},{"id":297228,"name":"Matthew Campbell","orcid":"0000-0003-3325-240X","position":10,"is_corresponding":false},{"id":1044888,"name":"Carla B. Roces","orcid":null,"position":11,"is_corresponding":false},{"id":1044442,"name":"Giulia Anderluzzi","orcid":"0000-0001-7363-9137","position":12,"is_corresponding":false},{"id":530640,"name":"Cameron Webb","orcid":"0000-0003-1029-5140","position":13,"is_corresponding":false},{"id":1044443,"name":"Yvonne Perrie","orcid":"0000-0001-8497-2541","position":14,"is_corresponding":false},{"id":1044444,"name":"Emma M. Creagh","orcid":"0000-0001-7631-4370","position":15,"is_corresponding":false},{"id":253532,"name":"Ed C. Lavelle","orcid":"0000-0002-3167-1080","position":16,"is_corresponding":false},{"id":253526,"name":"Natalia Muñoz‐Wolf","orcid":"0000-0002-5173-4026","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T01:08:28.266998Z","pmid":"36652908","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}