{"doi":"10.1016/j.cell.2023.11.002","title":"Early cellular mechanisms of type I interferon-driven susceptibility to tuberculosis","abstract":"Mycobacterium tuberculosis (Mtb) causes 1.6 million deaths annually. Active tuberculosis correlates with a neutrophil-driven type I interferon (IFN) signature, but the cellular mechanisms underlying tuberculosis pathogenesis remain poorly understood. We found that interstitial macrophages (IMs) and plasmacytoid dendritic cells (pDCs) are dominant producers of type I IFN during Mtb infection in mice and non-human primates, and pDCs localize near human Mtb granulomas. Depletion of pDCs reduces Mtb burdens, implicating pDCs in tuberculosis pathogenesis. During IFN-driven disease, we observe abundant DNA-containing neutrophil extracellular traps (NETs) described to activate pDCs. Cell-type-specific disruption of the type I IFN receptor suggests that IFNs act on IMs to inhibit Mtb control. Single-cell RNA sequencing (scRNA-seq) indicates that type I IFN-responsive cells are defective in their response to IFNγ, a cytokine critical for Mtb control. We propose that pDC-derived type I IFNs act on IMs to permit bacterial replication, driving further neutrophil recruitment and active tuberculosis disease.","journal":"Cell","year":2023,"id":315728,"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":139,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"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":989422,"name":"Ophelia V. Lee","orcid":"0000-0002-3940-7807","position":1,"is_corresponding":false},{"id":989423,"name":"Stefan A. Fattinger","orcid":"0000-0003-4899-4414","position":2,"is_corresponding":false},{"id":720263,"name":"Charlotte A. Langner","orcid":"0000-0002-7817-3214","position":3,"is_corresponding":false},{"id":989424,"name":"Jaresley V. Guillen","orcid":"0000-0002-2529-2543","position":4,"is_corresponding":false},{"id":91618,"name":"Joshua M. Peters","orcid":"0000-0001-9163-6706","position":5,"is_corresponding":false},{"id":989903,"name":"Andres Moon","orcid":null,"position":6,"is_corresponding":false},{"id":517390,"name":"Eileen M. Burd","orcid":"0000-0002-7055-942X","position":7,"is_corresponding":false},{"id":556929,"name":"Kristen C. Witt","orcid":"0000-0001-8744-9457","position":8,"is_corresponding":false},{"id":250993,"name":"Daniel B. Stetson","orcid":"0000-0002-5936-1113","position":9,"is_corresponding":false},{"id":449566,"name":"David L. Jaye","orcid":"0000-0001-7977-6909","position":10,"is_corresponding":false},{"id":91622,"name":"Bryan D. Bryson","orcid":"0000-0003-1716-6712","position":11,"is_corresponding":false},{"id":251793,"name":"Russell E. Vance","orcid":"0000-0002-6686-3912","position":12,"is_corresponding":false},{"id":556930,"name":"Dmitri I. Kotov","orcid":"0000-0001-7843-1503","position":0,"is_corresponding":true}],"reference_count":116,"raw_metadata":null,"created_at":"2026-07-19T01:06:32.274501Z","pmid":"38029747","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":[]}