{"doi":"10.1016/j.ebiom.2023.104678","title":"IFN-γ independent markers of Mycobacterium tuberculosis exposure among male South African gold miners","abstract":"BACKGROUND: The prevalence of tuberculosis among men who work in the gold mines of South Africa is among the highest in the world, but a fraction of miners demonstrate consistently negative results upon tuberculin skin test (TST) and IFN-γ release assay (IGRA). We hypothesized that these \"resisters\" (RSTRs) may display unconventional immune signatures of exposure to M. tuberculosis (M.tb). METHODS: In a cohort of RSTRs and matched controls with latent TB infection (LTBI), we profiled the functional breadth of M.tb antigen-specific T cell and antibody responses using multi-parameter flow cytometry and systems serology, respectively. FINDINGS: RSTRs and LTBI controls both exhibited IFN-γ independent T-cell and IgG antibody responses to M.tb-specific antigens ESAT-6 and CFP-10. Antigen-specific antibody Fc galactosylation and sialylation were higher among RSTRs. In a combined T-cell and antibody analysis, M.tb lysate-stimulated TNF secretion by T cells correlated positively with levels of purified protein derivative-specific IgG. A multivariate model of the combined data was able to differentiate RSTR and LTBI subjects. INTERPRETATION: IFN-γ independent immune signatures of exposure to M.tb, which are not detected by approved clinical diagnostics, are readily detectable in an occupational cohort uniquely characterized by intense and long-term infection pressure. Further, TNF may mediate a coordinated response between M.tb-specific T-cells and B-cells. FUNDING: This work was supported by the US National Institutes of Health (R01-AI124348 to Boom, Stein, and Hawn; R01-AI125189 and R01-AI146072 to Seshadri; and 75N93019C00071 to Fortune, Alter, Seshadri, and Boom), the Doris Duke Charitable Foundation (Davies), the Bill & Melinda Gates Foundation (OPP1151836 and OPP1109001 to Hawn; and OPP1151840 to Alter), Mass Life Science Foundation (Fortune), and Good Ventures Fund (Fortune).","journal":"EBioMedicine","year":2023,"id":326571,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"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":664158,"name":"Malisa T. Smith","orcid":null,"position":1,"is_corresponding":false},{"id":663368,"name":"Deniz Cizmeci","orcid":"0000-0003-3231-7726","position":2,"is_corresponding":false},{"id":106724,"name":"Stephanie Fischinger","orcid":"0000-0003-2307-3379","position":3,"is_corresponding":false},{"id":989736,"name":"Jessica Shih-Lu Lee","orcid":null,"position":4,"is_corresponding":false},{"id":297926,"name":"Lenette L. Lu","orcid":"0000-0003-4658-1261","position":5,"is_corresponding":false},{"id":571546,"name":"Erik D. Layton","orcid":"0000-0001-6409-290X","position":6,"is_corresponding":false},{"id":274995,"name":"Alison D. Grant","orcid":"0000-0002-2437-5195","position":7,"is_corresponding":false},{"id":231904,"name":"Katherine Fielding","orcid":"0000-0002-6524-3754","position":8,"is_corresponding":false},{"id":231947,"name":"Catherine M. Stein","orcid":"0000-0002-9763-5023","position":9,"is_corresponding":false},{"id":231891,"name":"W. Henry Boom","orcid":"0000-0001-5760-9595","position":10,"is_corresponding":false},{"id":445178,"name":"Thomas R. Hawn","orcid":"0000-0003-2368-3185","position":11,"is_corresponding":false},{"id":91624,"name":"Sarah M. Fortune","orcid":"0000-0001-7565-9975","position":12,"is_corresponding":false},{"id":573481,"name":"Robert S. Wallis","orcid":"0000-0001-6152-5183","position":13,"is_corresponding":false},{"id":432140,"name":"Gavin Churchyard","orcid":"0000-0002-4269-3699","position":14,"is_corresponding":false},{"id":106757,"name":"Galit Alter","orcid":"0000-0002-7680-9215","position":15,"is_corresponding":false},{"id":377302,"name":"Chetan Seshadri","orcid":"0000-0003-2783-7540","position":16,"is_corresponding":false},{"id":453396,"name":"Leela Davies","orcid":"0000-0003-4780-0606","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:08:33.106703Z","pmid":"37379655","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":[]}