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Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants

Author

Listed:
  • Iman Satti

    (University of Oxford)

  • Rachel E. Wittenberg

    (University of Oxford)

  • Shuailin Li

    (University of Oxford)

  • Stephanie A. Harris

    (University of Oxford)

  • Rachel Tanner

    (University of Oxford)

  • Deniz Cizmeci

    (University of Oxford)

  • Ashley Jacobs

    (University of Oxford
    University of Cape Town, Observatory)

  • Nicola Williams

    (University of Oxford, Radcliffe Observatory Quarter)

  • Humphrey Mulenga

    (University of Cape Town)

  • Helen A. Fletcher

    (London School of Hygiene & Tropical Medicine)

  • Thomas J. Scriba

    (University of Cape Town)

  • Michele Tameris

    (University of Cape Town)

  • Mark Hatherill

    (University of Cape Town)

  • Helen McShane

    (University of Oxford)

Abstract

Tuberculosis vaccine development is hindered by the lack of validated immune correlates of protection. Exploring immune correlates of risk of disease and/or infection in prospective samples can inform this field. We investigate whether previously identified immune correlates of risk of TB disease also associate with increased risk of M.tb infection in BCG-vaccinated South African infants, who became infected with M.tb during 2-3 years of follow-up. M.tb infection is defined by conversion to positive reactivity in the QuantiFERON test. We demonstrate that inflammation and immune activation are associated with risk of M.tb infection. Ag85A-specific IgG is elevated in infants that were subsequently infected with M.tb, and this is coupled with upregulated gene expression of immunoglobulin-associated genes and type-I interferon. Plasma levels of IFN- $$\alpha$$ α 2, TNF- $$\alpha$$ α , CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with M.tb.

Suggested Citation

  • Iman Satti & Rachel E. Wittenberg & Shuailin Li & Stephanie A. Harris & Rachel Tanner & Deniz Cizmeci & Ashley Jacobs & Nicola Williams & Humphrey Mulenga & Helen A. Fletcher & Thomas J. Scriba & Mich, 2022. "Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34061-7
    DOI: 10.1038/s41467-022-34061-7
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    References listed on IDEAS

    as
    1. Helen A. Fletcher & Margaret A. Snowden & Bernard Landry & Wasima Rida & Iman Satti & Stephanie A. Harris & Magali Matsumiya & Rachel Tanner & Matthew K. O’Shea & Veerabadran Dheenadhayalan & Leah Bog, 2016. "Correction: Corrigendum: T-cell activation is an immune correlate of risk in BCG vaccinated infants," Nature Communications, Nature, vol. 7(1), pages 1-1, September.
    2. Hector Sanz & John J Aponte & Jaroslaw Harezlak & Yan Dong & Aintzane Ayestaran & Augusto Nhabomba & Maxmillian Mpina & Obiang Régis Maurin & Núria Díez-Padrisa & Ruth Aguilar & Gemma Moncunill & Agna, 2017. "drLumi: An open-source package to manage data, calibrate, and conduct quality control of multiplex bead-based immunoassays data analysis," PLOS ONE, Public Library of Science, vol. 12(11), pages 1-18, November.
    3. Helen A. Fletcher & Margaret A. Snowden & Bernard Landry & Wasima Rida & Iman Satti & Stephanie A. Harris & Magali Matsumiya & Rachel Tanner & Matthew K. O’Shea & Veerabadran Dheenadhayalan & Leah Bog, 2016. "T-cell activation is an immune correlate of risk in BCG vaccinated infants," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
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