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IFN-γ independent markers of Mycobacterium tuberculosis exposure among male South African gold miners.
Davies, Leela R L; Smith, Malisa T; Cizmeci, Deniz; Fischinger, Stephanie; Shih-Lu Lee, Jessica; Lu, Lenette L; Layton, Erik D; Grant, Alison D; Fielding, Katherine; Stein, Catherine M; Boom, W Henry; Hawn, Thomas R; Fortune, Sarah M; Wallis, Robert S; Churchyard, Gavin J; Alter, Galit; Seshadri, Chetan.
Afiliación
  • Davies LRL; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Brigham and Women's Hospital, Boston, MA, USA.
  • Smith MT; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
  • Cizmeci D; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Fischinger S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Shih-Lu Lee J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Lu LL; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Layton ED; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
  • Grant AD; TB Centre, London School of Hygiene and Tropical Medicine, London, UK.
  • Fielding K; TB Centre, London School of Hygiene and Tropical Medicine, London, UK.
  • Stein CM; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Department of Population & Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Boom WH; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Hawn TR; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
  • Fortune SM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA.
  • Wallis RS; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; The Aurum Institute, Parktown, South Africa.
  • Churchyard GJ; The Aurum Institute, Parktown, South Africa; Department of Medicine, Vanderbilt University, Nashville, TN, USA.
  • Alter G; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Moderna Therapeutics, Cambridge, MA, USA.
  • Seshadri C; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA; Seattle Tuberculosis Research Advancement Center, Seattle, WA, USA. Electronic address: seshadri@u.washington.edu.
EBioMedicine ; 93: 104678, 2023 Jul.
Article en En | MEDLINE | ID: mdl-37379655
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).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 2_ODS3 / 3_ND Problema de salud: 2_enfermedades_transmissibles / 3_neglected_diseases / 3_tuberculosis Asunto principal: Tuberculosis / Mycobacterium tuberculosis Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male País/Región como asunto: Africa Idioma: En Revista: EBioMedicine Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 2_ODS3 / 3_ND Problema de salud: 2_enfermedades_transmissibles / 3_neglected_diseases / 3_tuberculosis Asunto principal: Tuberculosis / Mycobacterium tuberculosis Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male País/Región como asunto: Africa Idioma: En Revista: EBioMedicine Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos