{"doi":"10.1101/2023.10.27.564420","title":"Interleukin-1 receptor antagonist is a conserved early factor for exacerbating tuberculosis susceptibility","abstract":"Summary Mycobacterium tuberculosis ( Mtb ) causes 1.25 million deaths a year. However, tuberculosis (TB) pathogenesis remains poorly understood and is not fully recapitulated in standard mouse models. Here we find that gene signatures from three different Mtb -susceptible mouse models predict active TB disease in humans significantly better than a signature from resistant C57BL/6 (B6) mice. Conserved among susceptible mice, non-human primates, and humans, but largely absent from B6 mice, was Mtb -induced differentiation of macrophages into an Spp1 + differentiation state. Spp1 + macrophages expressed high levels of immunosuppressive molecules including IL-1 receptor antagonist (IL-1Ra). IL-1Ra was previously reported to cause Mtb susceptibility in one mouse model, but whether IL-1Ra is broadly important remains uncertain. Here we report that enhancement of IL-1 signaling via deletion of IL-Ra promoted bacterial control across three susceptible mouse models. We found IL-1 signaling amplified production of multiple cytokines by lymphoid and stromal cells, providing a multifactorial mechanism for how IL-1 promotes Mtb control. Our results indicate that myeloid cell expression of immunosuppressive molecules, in particular IL-1 receptor antagonist, is a conserved early mechanism limiting Mtb control in mice, non-human primates, and humans.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390613,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"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":556928,"name":"Daisy X. Ji","orcid":"0000-0002-9148-3620","position":1,"is_corresponding":false},{"id":245278,"name":"Bruce A. Rosa","orcid":"0000-0002-6820-446X","position":2,"is_corresponding":false},{"id":449566,"name":"David L. Jaye","orcid":"0000-0001-7977-6909","position":3,"is_corresponding":false},{"id":252291,"name":"Sara Suliman","orcid":"0000-0002-5154-576X","position":4,"is_corresponding":false},{"id":29027,"name":"Makedonka Mitreva","orcid":"0000-0001-9572-3436","position":5,"is_corresponding":false},{"id":1040605,"name":"Cem Gabay","orcid":"0000-0001-6853-3063","position":6,"is_corresponding":false},{"id":251793,"name":"Russell E. Vance","orcid":"0000-0002-6686-3912","position":7,"is_corresponding":false},{"id":556930,"name":"Dmitri I. Kotov","orcid":"0000-0001-7843-1503","position":8,"is_corresponding":false},{"id":989422,"name":"Ophelia V. Lee","orcid":"0000-0002-3940-7807","position":0,"is_corresponding":true}],"reference_count":141,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:37.743462Z","pmid":"37961447","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":[]}