| Autor: |
Tomalka J, Sharma A, Smith AGC, Avaliani T, Gujabidze M, Bakuradze T, Sabanadze S, Jones DP, Avaliani Z, Kipiani M, Kempker RR, Collins JM |
| Jazyk: |
angličtina |
| Zdroj: |
MedRxiv : the preprint server for health sciences [medRxiv] 2023 Jun 29. Date of Electronic Publication: 2023 Jun 29. |
| DOI: |
10.1101/2023.06.26.23291676 |
| Abstrakt: |
Much of the high mortality in tuberculosis meningitis (TBM) is attributable to excessive inflammation, making it imperative to identify targets for host-directed therapies that reduce pathologic inflammation and mortality. In this study, we investigate how cytokines and metabolites in the cerebral spinal fluid (CSF) associate with TBM at diagnosis and during TBM treatment. At diagnosis, TBM patients demonstrate significant increases versus controls of cytokines and chemokines that promote inflammation and cell migration including IL-17A, IL-2, TNFα, IFNγ, and IL-1β. Inflammatory immune signaling was strongly correlated with immunomodulatory metabolites including kynurenine, lactic acid, carnitine, tryptophan, and itaconate. Inflammatory immunometabolic networks were only partially reversed with two months of effective TBM treatment and remained significantly different versus control CSF. Together, these data highlight a critical role for host metabolism in regulating the inflammatory response to TBM and indicate the timeline for restoration of immune homeostasis in the CSF is prolonged. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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