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Tuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity

Author

Listed:
  • Ursula K. Rohlwink

    (University of Cape Town
    University of Cape Town)

  • Anthony Figaji

    (University of Cape Town)

  • Katalin A. Wilkinson

    (University of Cape Town
    The Francis Crick Institute)

  • Stuart Horswell

    (The Francis Crick Institute)

  • Abdul K. Sesay

    (The Francis Crick Institute
    Genomics Core, MRC Unit The Gambia at LSHTM)

  • Armin Deffur

    (University of Cape Town)

  • Nico Enslin

    (University of Cape Town)

  • Regan Solomons

    (Stellenbosch University)

  • Ronald Toorn

    (Stellenbosch University)

  • Brian Eley

    (University of Cape Town)

  • Michael Levin

    (Imperial College London)

  • Robert J. Wilkinson

    (University of Cape Town
    The Francis Crick Institute
    University of Cape Town
    Imperial College London)

  • Rachel P. J. Lai

    (The Francis Crick Institute
    Imperial College London)

Abstract

Tuberculous meningitis (TBM) is the most severe form of TB with high rates of mortality and morbidity. Here we conduct RNA-sequencing on whole blood as well as on ventricular and lumbar cerebrospinal fluid (CSF) of pediatric patients treated for TBM. Differential transcript expression of TBM cases are compared with healthy controls in whole blood and with non-TB cerebral infection controls in CSF. Whole blood RNA-Seq analysis demonstrates a distinct immune response pattern in TBM, with significant increase in both canonical and non-canonical inflammasome activation and decrease in T-cell activation. In ventricular CSF, a significant enrichment associated with neuronal excitotoxicity and cerebral damage is detected in TBM. Finally, compartmental comparison in TBM indicates that the ventricular profile represents brain injury whereas the lumbar profile represents protein translation and cytokine signaling. Together, transcriptomic analysis shows that disease processes differ between the periphery and the central nervous system, and within brain compartments.

Suggested Citation

  • Ursula K. Rohlwink & Anthony Figaji & Katalin A. Wilkinson & Stuart Horswell & Abdul K. Sesay & Armin Deffur & Nico Enslin & Regan Solomons & Ronald Toorn & Brian Eley & Michael Levin & Robert J. Wilk, 2019. "Tuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11783-9
    DOI: 10.1038/s41467-019-11783-9
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