{"doi":"10.4049/jimmunol.204.supp.227.30","title":"Gasdermin D Promotes AIM2 Inflammasome Activation and Is Required for Host Protection against Francisella novicida","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The DNA sensor absent in melanoma 2 (AIM2) forms an inflammasome complex with ASC and caspase-1 in response to Francisella tularensis subspecies novicida infection, leading to maturation of IL-1b and IL-18 and pyroptosis. AIM2 is critical for host protection against F. novicida infection in vivo; however, the role of pyroptosis downstream of the AIM2 inflammasome is unknown. Recent studies have identified gasdermin D (GSDMD) as the molecule executing pyroptosis by forming pores on the plasma membrane following activation by inflammatory caspase-1 and -11. In this study, we report that GSDMD-deficient mice were susceptible to F. novicida infection compared with wild type mice. Interestingly, we observed that GSDMD is required for optimal caspase-1 activation and pyroptotic cell death in F. novicida–infected bone marrow–derived macrophages. Furthermore, caspase-1 activation was compromised in bone marrow–derived macrophages lacking GSDMD stimulated with other AIM2 inflammasome triggers, including poly(dA:dT) transfection and mouse CMV infection. Overall, our study highlights a function, to our knowledge previously unknown, for GSDMD in promoting caspase-1 activation by AIM2 inflammasome.</jats:p>","journal":"The Journal of Immunology","year":2020,"id":594724,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1522589,"name":"Qi Fan Zhu","orcid":null,"position":1,"is_corresponding":false},{"id":408139,"name":"Arjun Balakrishnan","orcid":null,"position":2,"is_corresponding":false},{"id":105431,"name":"Rajendra Karki","orcid":"0000-0003-4436-9128","position":3,"is_corresponding":false},{"id":1514524,"name":"Thirumala-Devi Kanneganti","orcid":null,"position":4,"is_corresponding":false},{"id":1522588,"name":"Min zheng","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Gasdermin D Promotes AIM2 Inflammasome Activation and Is Required for Host Protection against Francisella novicida","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The DNA sensor absent in melanoma 2 (AIM2) forms an inflammasome complex with ASC and caspase-1 in response to Francisella tularensis subspecies novicida infection, leading to maturation of IL-1b and IL-18 and pyroptosis. AIM2 is critical for host protection against F. novicida infection in vivo; however, the role of pyroptosis downstream of the AIM2 inflammasome is unknown. Recent studies have identified gasdermin D (GSDMD) as the molecule executing pyroptosis by forming pores on the plasma membrane following activation by inflammatory caspase-1 and -11. In this study, we report that GSDMD-deficient mice were susceptible to F. novicida infection compared with wild type mice. Interestingly, we observed that GSDMD is required for optimal caspase-1 activation and pyroptotic cell death in F. novicida–infected bone marrow–derived macrophages. Furthermore, caspase-1 activation was compromised in bone marrow–derived macrophages lacking GSDMD stimulated with other AIM2 inflammasome triggers, including poly(dA:dT) transfection and mouse CMV infection. Overall, our study highlights a function, to our knowledge previously unknown, for GSDMD in promoting caspase-1 activation by AIM2 inflammasome.</jats:p>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23304386","pmcid":null,"openalex_id":"https://openalex.org/W4313369147","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2024,"count":2}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/jimmunol/article/204/1_Supplement/227.30/7949562","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.204.supp.227.30","host_type":"journal"}],"fields_of_study":["Inflammasome and immune disorders","Genital Health and Disease","IL-33, ST2, and ILC Pathways"],"mesh_terms":[],"keywords":["Pyroptosis","AIM2","Inflammasome","Francisella","Caspase 1","Francisella tularensis","Biology","Cell biology","Microbiology","Chemistry","Immunology","Inflammation","Biochemistry","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T15:24:27.748863Z","pmid":null,"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":[]}