{"doi":"10.1016/j.celrep.2024.114004","title":"A bacterial toxin co-opts caspase-3 to disable active gasdermin D and limit macrophage pyroptosis","abstract":"During infections, host cells are exposed to pathogen-associated molecular patterns (PAMPs) and virulence factors that stimulate multiple signaling pathways that interact additively, synergistically, or antagonistically. The net effect of such higher-order interactions is a vital determinant of the outcome of host-pathogen interactions. Here, we demonstrate one such complex interplay between bacterial exotoxin- and PAMP-induced innate immune pathways. We show that two caspases activated during enterohemorrhagic Escherichia coli (EHEC) infection by lipopolysaccharide (LPS) and Shiga toxin (Stx) interact in a functionally antagonistic manner; cytosolic LPS-activated caspase-11 cleaves full-length gasdermin D (GSDMD), generating an active pore-forming N-terminal fragment (NT-GSDMD); subsequently, caspase-3 activated by EHEC Stx cleaves the caspase-11-generated NT-GSDMD to render it nonfunctional, thereby inhibiting pyroptosis and interleukin-1β maturation. Bacteria typically subvert inflammasomes by targeting upstream components such as NLR sensors or full-length GSDMD but not active NT-GSDMD. Thus, our findings uncover a distinct immune evasion strategy where a bacterial toxin disables active NT-GSDMD by co-opting caspase-3.","journal":"Cell Reports","year":2024,"id":424550,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":490108,"name":"Chengliang Wang","orcid":"0000-0001-5249-4856","position":1,"is_corresponding":false},{"id":461624,"name":"Atri Ta","orcid":"0000-0001-8282-6073","position":2,"is_corresponding":false},{"id":490107,"name":"Morena S. Havira","orcid":"0000-0001-8683-4820","position":3,"is_corresponding":false},{"id":490109,"name":"Jianbin Ruan","orcid":"0000-0001-5843-8273","position":4,"is_corresponding":false},{"id":240695,"name":"Vijay Rathinam","orcid":"0000-0002-8009-3977","position":5,"is_corresponding":false},{"id":461625,"name":"Sivapriya Kailasan Vanaja","orcid":"0000-0001-6188-2869","position":6,"is_corresponding":false},{"id":651464,"name":"Skylar S. Wright","orcid":"0000-0002-1341-5710","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T01:58:21.523756Z","pmid":"38522070","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":[]}