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

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dc.contributor.authorRohlwink, Ursula K.en_ZA
dc.contributor.authorFigaji, Anthonyen_ZA
dc.contributor.authorWilkinson, Katalin A.en_ZA
dc.contributor.authorHorswell, Stuarten_ZA
dc.contributor.authorSesay, Abdul K.en_ZA
dc.contributor.authorDeffur, Arminen_ZA
dc.contributor.authorEnslin, Nicoen_ZA
dc.contributor.authorSolomons, Reganen_ZA
dc.contributor.authorVan Toorn, Ronalden_ZA
dc.contributor.authorEley, Brianen_ZA
dc.contributor.authorLevin, Michaelen_ZA
dc.contributor.authorWilkinson, Robert J.en_ZA
dc.contributor.authorLai, Rachel P. J.en_ZA
dc.date.accessioned2021-10-06T14:25:50Z
dc.date.available2021-10-06T14:25:50Z
dc.date.issued2019
dc.descriptionCITATION: 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.
dc.descriptionThe original publication is available at https://www.nature.com
dc.description.abstractENGLISH 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.en_ZA
dc.description.urihttps://www.nature.com/articles/s41467-019-11783-9
dc.description.versionPublisher's version
dc.format.extent8 pagesen_ZA
dc.identifier.citationRohlwink, 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
dc.identifier.issn2041-1723 (online)
dc.identifier.otherdoi:10.1038/s41467-019-11783-9
dc.identifier.urihttp://hdl.handle.net/10019.1/123150
dc.language.isoen_ZAen_ZA
dc.publisherNature Research (part of Springer Nature)en_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculous meningitisen_ZA
dc.subjectTuberculosis in childrenen_ZA
dc.subjectCompartmental analysis (Biology)en_ZA
dc.subjectAnalysis, Nucleic acid sequenceen_ZA
dc.subjectCerebrospinal fluid -- Examinationen_ZA
dc.titleTuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicityen_ZA
dc.typeArticleen_ZA
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