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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.
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1 Neuroscience Institute, Division of Neurosurgery, University of Cape Town, Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
2 Neuroscience Institute, Division of Neurosurgery, University of Cape Town, Cape Town, South Africa
3 Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; The Francis Crick Institute, London, UK
4 The Francis Crick Institute, London, UK
5 The Francis Crick Institute, London, UK; Genomics Core, MRC Unit The Gambia at LSHTM, Serrekunda, The Gambia
6 Department of Medicine, University of Cape Town, Cape Town, South Africa
7 Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa
8 Paediatric Infectious Diseases Unit, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa
9 Department of Infectious Disease, Imperial College London, London, UK
10 Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; The Francis Crick Institute, London, UK; Department of Medicine, University of Cape Town, Cape Town, South Africa; Department of Infectious Disease, Imperial College London, London, UK
11 The Francis Crick Institute, London, UK; Department of Infectious Disease, Imperial College London, London, UK