An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis

被引:1426
作者
Berry, Matthew P. R. [1 ]
Graham, Christine M. [1 ]
McNab, Finlay W. [1 ]
Xu, Zhaohui [6 ]
Bloch, Susannah A. A. [3 ]
Oni, Tolu [4 ,5 ]
Wilkinson, Katalin A. [2 ,4 ]
Banchereau, Romain [9 ]
Skinner, Jason [6 ]
Wilkinson, Robert J. [2 ,4 ]
Quinn, Charles [6 ]
Blankenship, Derek [7 ]
Dhawan, Ranju [8 ]
Cush, John J. [6 ]
Mejias, Asuncion [10 ]
Ramilo, Octavio [10 ]
Kon, Onn M. [3 ]
Pascual, Virginia [6 ]
Banchereau, Jacques [6 ]
Chaussabel, Damien [6 ]
O'Garra, Anne [1 ]
机构
[1] Natl Inst Med Res, MRC, Div Immunoregulat, London NW7 1AA, England
[2] Natl Inst Med Res, MRC, Div Mycobacterial Res, London NW7 1AA, England
[3] Imperial Coll Healthcare NHS Trust, St Marys Hosp, Dept Resp Med, London W2 1NY, England
[4] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Observatory, South Africa
[5] Univ London Imperial Coll Sci Technol & Med, Wright Fleming Inst, Div Med, London W2 1PG, England
[6] ANRS Ctr Human Vaccines, INSERM, U899, Baylor Inst Immunol Res, Dallas, TX 75204 USA
[7] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX 75206 USA
[8] Imperial Coll Healthcare NHS Trust, St Marys Hosp, Dept Radiol, London W2 1NY, England
[9] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA
[10] Nationwide Childrens Hosp, Ctr Vaccines & Immun, Res Inst, Columbus, OH 43205 USA
基金
英国医学研究理事会; 美国国家卫生研究院;
关键词
GENE-EXPRESSION PATTERNS; MYCOBACTERIUM-TUBERCULOSIS; INFECTION; RESPONSES; IMMUNITY; CELLS;
D O I
10.1038/nature09247
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Efforts to control it are hampered by difficulties with diagnosis, prevention and treatment(1,2). Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease. Current tests, however, cannot identify which individuals will develop disease(3). The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines(4,5). Here we identify a whole-blood 393 transcript signature for active TB in intermediate and high-burden settings, correlating with radiological extent of disease and reverting to that of healthy controls after treatment. A subset of patients with latent TB had signatures similar to those in patients with active TB. We also identify a specific 86-transcript signature that discriminates active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-gamma and type I IFN-alpha beta signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis suggest that this TB signature reflects changes in cellular composition and altered gene expression. Although an IFN-inducible signature was also observed in whole blood of patients with systemic lupus erythematosus (SLE), their complete modular signature differed from TB, with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto underappreciated role of type I IFN-alpha beta signalling in the pathogenesis of TB, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic.
引用
收藏
页码:973 / U98
页数:7
相关论文
共 30 条
  • [1] Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade
    Allantaz, Florence
    Chaussabel, Damien
    Stichweh, Dorothee
    Bennett, Lynda
    Allman, Windy
    Mejias, Asuncion
    Ardura, Monica
    Chung, Wendy
    Wise, Carol
    Palucka, Karolina
    Ramilo, Octavio
    Punaro, Marilynn
    Banchereau, Jacques
    Pascual, Virginia
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (09) : 2131 - 2144
  • [2] Enhanced Monocyte Response and Decreased Central Memory T Cells in Children with Invasive Staphylococcus aureus Infections
    Ardura, Monica I.
    Banchereau, Romain
    Mejias, Asuncion
    Di Pucchio, Tiziana
    Glaser, Casey
    Allantaz, Florence
    Pascual, Virginia
    Banchereau, Jacques
    Chaussabel, Damien
    Ramilo, Octavio
    [J]. PLOS ONE, 2009, 4 (05):
  • [3] Blood Monocytes: Development, Heterogeneity, and Relationship with Dendritic Cells
    Auffray, Cedric
    Sieweke, Michael H.
    Geissmann, Frederic
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2009, 27 : 669 - 692
  • [4] Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus
    Baechler, EC
    Batliwalla, FM
    Karypis, G
    Gaffney, PM
    Ortmann, WA
    Espe, KJ
    Shark, KB
    Grande, WJ
    Hughes, KM
    Kapur, V
    Gregersen, PK
    Behrens, TW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) : 2610 - 2615
  • [5] The spectrum of latent tuberculosis: rethinking the biology and intervention strategies
    Barry, Clifton E., III
    Boshoff, Helena I.
    Dartois, Veronique
    Dick, Thomas
    Ehrt, Sabine
    Flynn, JoAnne
    Schnappinger, Dirk
    Wilkinson, Robert J.
    Young, Douglas
    [J]. NATURE REVIEWS MICROBIOLOGY, 2009, 7 (12) : 845 - 855
  • [6] BECK JS, 1985, CLIN EXP IMMUNOL, V60, P49
  • [7] Interferon and granulopoiesis signatures in systemic lupus erythematosus blood
    Bennett, L
    Palucka, AK
    Arce, E
    Cantrell, V
    Borvak, J
    Banchereau, J
    Pascual, V
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (06) : 711 - 723
  • [8] Genetic dissection of immunity to mycobacteria: The human model
    Casanova, JL
    Abel, L
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 : 581 - 620
  • [9] A modular analysis framework for blood genomics studies: Application to systemic lupus erythematosus
    Chaussabel, Damien
    Quinn, Charles
    Shen, Jing
    Patel, Pinakeen
    Glaser, Casey
    Baldwin, Nicole
    Stichweh, Dorothee
    Blankenship, Derek
    Li, Lei
    Munagala, Indira
    Bennett, Lynda
    Allantaz, Florence
    Mejias, Asuncion
    Ardura, Monica
    Kaizer, Ellen
    Monnet, Laurence
    Allman, Windy
    Randall, Henry
    Johnson, Diane
    Lanier, Aimee
    Punaro, Marilynn
    Wittkowski, Knut M.
    White, Perrin
    Fay, Joseph
    Klintmalm, Goran
    Ramilo, Octavio
    Palucka, A. Karolina
    Banchereau, Jacques
    Pascual, Virginia
    [J]. IMMUNITY, 2008, 29 (01) : 150 - 164
  • [10] Expression of the nitric oxide synthase 2 gene is not essential for early control of Mycobacterium tuberculosis in the murine lung
    Cooper, AM
    Pearl, JE
    Brooks, JV
    Ehlers, S
    Orme, IM
    [J]. INFECTION AND IMMUNITY, 2000, 68 (12) : 6879 - 6882