{"doi":"10.3389/fimmu.2021.755961","title":"Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity","abstract":"Non-canonical inflammasome activation by mouse caspase-11 (or human CASPASE-4/5) is crucial for the clearance of certain gram-negative bacterial infections, but can lead to severe inflammatory damage. Factors that promote non-canonical inflammasome activation are well recognized, but less is known about the mechanisms underlying its negative regulation. Herein, we identify that the caspase-11 inflammasome in mouse and human macrophages (Mϕ) is negatively controlled by the zinc (Zn 2+ ) regulating protein, metallothionein 3 (MT3). Upon challenge with intracellular lipopolysaccharide (iLPS), Mϕ increased MT3 expression that curtailed the activation of caspase-11 and its downstream targets caspase-1 and interleukin (IL)-1β. Mechanistically, MT3 increased intramacrophage Zn 2+ to downmodulate the TRIF-IRF3-STAT1 axis that is prerequisite for caspase-11 effector function. In vivo , MT3 suppressed activation of the caspase-11 inflammasome, while caspase-11 and MT3 synergized in impairing antibacterial immunity. The present study identifies an important yin-yang relationship between the non-canonical inflammasome and MT3 in controlling inflammation and immunity to gram-negative bacteria.","journal":"Frontiers in Immunology","year":2021,"id":183061,"datarank":0.6742801678754008,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.26807263771006923,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.26807263771006923,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":14,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":736147,"name":"Jason C. Gardner","orcid":"0000-0002-5924-9201","position":1,"is_corresponding":false},{"id":736148,"name":"Abhijit Satpati","orcid":"0000-0003-2674-7973","position":2,"is_corresponding":false},{"id":687876,"name":"Suba Nookala","orcid":"0000-0002-4632-265X","position":3,"is_corresponding":false},{"id":688610,"name":"Santhosh Mukundan","orcid":null,"position":4,"is_corresponding":false},{"id":312137,"name":"Aleksey Porollo","orcid":"0000-0002-3202-5099","position":5,"is_corresponding":false},{"id":724354,"name":"Julio A. Landero Figueroa","orcid":"0000-0001-8641-0497","position":6,"is_corresponding":false},{"id":736149,"name":"Kavitha Subramanian Vignesh","orcid":"0000-0002-2943-2988","position":7,"is_corresponding":false},{"id":736731,"name":"Debabrata Chowdhury","orcid":null,"position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:48:17.816498Z","pmid":"34867993","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":[]}