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

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. Wilkinson and Rachel P. J. Lai ()
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Ursula K. Rohlwink: University of Cape Town
Anthony Figaji: University of Cape Town
Katalin A. Wilkinson: University of Cape Town
Stuart Horswell: The Francis Crick Institute
Abdul K. Sesay: The Francis Crick Institute
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
Rachel P. J. Lai: The Francis Crick Institute

Nature Communications, 2019, vol. 10, issue 1, 1-8

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11783-9

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