MMPs and NETs are detrimental in CNS-tuberculosis with MMP Inhibition in CNS-tuberculosis mice improving survival.

ABSTRACT: Despite anti-tuberculous treatment (ATT), central nervous system tuberculosis (CNS-TB) still causes permanent neurological deficits and death. To identify prognostic factors, we profiled a prospective cohort of pediatric HIV-negative tuberculous meningitis (TBM) and non-TBM patients. We found significantly increased cerebrospinal fluid (CSF) matrix metalloproteinases (MMPs) and neutrophil extracellular traps (NETs) in TBM patients with neuroradiological abnormalities and poor outcomes. To dissect mechanisms, we used our existing CNS-TB murine model, which shows neutrophil-rich necrotizing pyogranulomas with MMP-9 and NETs colocalizing, as observed in human CNS-TB pathology. Spatial transcriptomic analysis of both human and murine CNS-TB demonstrates a highly-inflamed and neutrophil-rich mi

SUBMITTER: Poh XY 

PROVIDER: S-EPMC12514826 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature