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

ENGLISH 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.

Description

CITATION: Rohlwink, U. K., et al. 2019. Tuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity. Nature Communications, 10:3767, doi:10.1038/s41467-019-11783-9.
The original publication is available at https://www.nature.com

Keywords

Tuberculous meningitis, Tuberculosis in children, Compartmental analysis (Biology), Analysis, Nucleic acid sequence, Cerebrospinal fluid -- Examination

Citation

Rohlwink, U. K., et al. 2019. Tuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity. Nature Communications, 10:3767, doi:10.1038/s41467-019-11783-9

URI

http://hdl.handle.net/10019.1/123150

Collections

Research Articles (Paediatrics and Child Health)

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