{"doi":"10.1101/2021.08.25.457662","title":"A hierarchical GBP network promotes cytosolic LPS recognition and sepsis","abstract":"Abstract Bacterial lipopolysaccharide (LPS) is one of the most bioactive substances known. Trace amounts trigger robust immunity to infection but also life-threatening sepsis causing millions of deaths each year. LPS contamination of the cytosol elicits a caspase-dependent inflammasome pathway promoting cytokine release and host cell death. Here, we report an immune GTPase network controls multiple steps in this pathway by genome-engineering mice to lack 7 different guanylate-binding proteins (GBPs). Gbp2 - / - and Gbp3 - / - mice had severe caspase-11-driven defects that protected them from septic shock. Gbp2 recruited caspase-11 for LPS recognition whereas Gbp3 assembled and trafficked the pyroptotic pore-forming protein, gasdermin D, after caspase-11 cleavage. Together, our results identify a new functional hierarchy wherein different GBPs choreograph sequential steps in the non-canonical inflammasome pathway to control Gram-negative sepsis. One-Sentence Summary Immune GTPase network orchestrates hierarchical immunity to bacterial products in vivo","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214613,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"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":635240,"name":"Bae-Hoon Kim","orcid":"0000-0001-6866-7248","position":1,"is_corresponding":false},{"id":626032,"name":"Pradeep Kumar","orcid":"0000-0002-0892-5425","position":2,"is_corresponding":false},{"id":393234,"name":"Kyle Tretina","orcid":"0000-0002-1740-2730","position":3,"is_corresponding":false},{"id":635242,"name":"Agnieszka Mamińska","orcid":"0000-0002-1300-8242","position":4,"is_corresponding":false},{"id":367251,"name":"William M. Philbrick","orcid":"0000-0001-9219-8322","position":5,"is_corresponding":false},{"id":80236,"name":"Richard A. Flavell","orcid":"0000-0003-4461-0778","position":6,"is_corresponding":false},{"id":626033,"name":"John D. MacMicking","orcid":"0000-0002-1734-135X","position":7,"is_corresponding":false},{"id":808170,"name":"Eui‐Soon Park","orcid":"0000-0002-1375-8027","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:52:46.604690Z","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":[]}