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Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

  • Academic Journal
  • Scriba TJ; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Penn-Nicholson A; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Shankar S; The Center for Infectious Disease Research, Seattle, WA, United States of America.
    Hraha T; Somalogic Inc, Boulder, CO, United States of America.
    Thompson EG; The Center for Infectious Disease Research, Seattle, WA, United States of America.
    Sterling D; Somalogic Inc, Boulder, CO, United States of America.
    Nemes E; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Darboe F; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Suliman S; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Amon LM; The Center for Infectious Disease Research, Seattle, WA, United States of America.
    Mahomed H; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.; Now at Metro District Health Services, Western Cape Government: Health and Division of Public Health and Health Systems, Department of Global Health, Faculty of Health Sciences and Medicine, Stellenbosch University, Cape Town, South Africa.
    Erasmus M; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Whatney W; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Johnson JL; Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Cleveland Medical Center, Cleveland, OH, United States of America.
    Boom WH; Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Cleveland Medical Center, Cleveland, OH, United States of America.
    Hatherill M; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Valvo J; The Center for Infectious Disease Research, Seattle, WA, United States of America.
    De Groote MA; Somalogic Inc, Boulder, CO, United States of America.
    Ochsner UA; Somalogic Inc, Boulder, CO, United States of America.
    Aderem A; The Center for Infectious Disease Research, Seattle, WA, United States of America.
    Hanekom WA; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Zak DE; The Center for Infectious Disease Research, Seattle, WA, United States of America.
  • PLoS pathogens [PLoS Pathog] 2017 Nov 16; Vol. 13 (11), pp. e1006687. Date of Electronic Publication: 2017 Nov 16 (Print Publication: 2017).
  • English
  • Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis.
    Trial Registration: Clincialtrials.gov, NCT01119521.
Additional Information
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
Original Publication: San Francisco, CA : Public Library of Science, c2005-
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D43 TW000231 United States TW FIC NIH HHS; N01AI70022 United States AI NIAID NIH HHS; R01 AI087915 United States AI NIAID NIH HHS; N01AI95383 United States AI NIAID NIH HHS; U19 AI106761 United States AI NIAID NIH HHS
ClinicalTrials.gov NCT01119521
0 (Vaccines)
Date Created: 20171118 Date Completed: 20171207 Latest Revision: 20201214
20211214
PMC5689825
10.1371/journal.ppat.1006687
29145483
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