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 Van Toorn, Brian Eley, Michael Levin, Robert J Wilkinson, Rachel P J Lai
Author Information
Ursula K Rohlwink: Neuroscience Institute, Division of Neurosurgery, University of Cape Town, Cape Town, South Africa. ORCID
Anthony Figaji: Neuroscience Institute, Division of Neurosurgery, University of Cape Town, Cape Town, South Africa.
Katalin A Wilkinson: Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Stuart Horswell: The Francis Crick Institute, London, NW1 1AT, UK.
Abdul K Sesay: The Francis Crick Institute, London, NW1 1AT, UK.
Armin Deffur: Department of Medicine, University of Cape Town, Cape Town, South Africa.
Nico Enslin: Neuroscience Institute, Division of Neurosurgery, University of Cape Town, Cape Town, South Africa.
Regan Solomons: Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa.
Ronald Van Toorn: Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa.
Brian Eley: Paediatric Infectious Diseases Unit, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa. ORCID
Michael Levin: Department of Infectious Disease, Imperial College London, London, W2 1PG, UK.
Robert J Wilkinson: Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. ORCID
Rachel P J Lai: The Francis Crick Institute, London, NW1 1AT, UK. rachel.lai@imperial.ac.uk.
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.
