ArticleJournal of neuroinflammation2017
Complex regulation of neutrophil-derived MMP-9 secretion in central nervous system tuberculosis.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 62 citations in OpenAlex.
- Doxycycline host-directed therapy in human pulmonary tuberculosis.The Journal of clinical investigation · 2021Trial
- Epigenetic modulation in tuberculosis - mycobacterial defense mechanism to host immune responses.Frontiers in immunology · 2026Review
- MMPs and NETs are detrimental in CNS-tuberculosis with MMP Inhibition in CNS-tuberculosis mice improving survival.Journal of neuroinflammation · 2025Article
- Combined cerebrospinal fluid sCD163, MMP-9, with serum NCAM1 protein levels for predicting the prognosis of patients with tuberculous meningitis.Scientific reports · 2025Article
- Pathogenic role for CD101-negative neutrophils in the type I interferon-mediated immunopathogenesis of tuberculosis.Cell reports · 2025Article
- Association between systemic immune-inflammation index at admission and post-stroke depression in patients with acute ischemic stroke.Frontiers in neurology · 2025Article
- The association between neutrophil percentage-to-albumin ratio (NPAR) and depression among US adults: a cross-sectional study.Scientific reports · 2024Article
- Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia.Aging and disease · 2024Review
- Association between systemic immune-inflammation index and post-stroke depression: a cross-sectional study of the national health and nutrition examination survey 2005-2020.Frontiers in neurology · 2024Article
- Association between Systemic Immune Inflammation Index and Cognitive Impairment after Acute Ischemic Stroke.Brain sciences · 2023Article
- Blood-Brain Barrier Integrity Damage in Bacterial Meningitis: The Underlying Link, Mechanisms, and Therapeutic Targets.International journal of molecular sciences · 2023Review
- Mechanosensory feedback loops during chronic inflammation.Frontiers in cell and developmental biology · 2023Review
- Nos2Journal of neuroinflammation · 2022Article
- The role of neutrophils in the dysfunction of central nervous system barriers.Frontiers in aging neuroscience · 2022Review
- The Impact of Obesity on Microglial Function: Immune, Metabolic and Endocrine Perspectives.Cells · 2021Review
- GSK-3α/β Activity Negatively Regulates MMP-1/9 Expression to SuppressFrontiers in immunology · 2021Article
- The Association Between Systemic Inflammatory Markers and Post-Stroke Depression: A Prospective Stroke Cohort.Clinical interventions in aging · 2021Article
- Neutrophil-Mediated Immunopathology and Matrix Metalloproteinases in Central Nervous System - Tuberculosis.Frontiers in immunology · 2021Review
- Review
- Transcriptome profiling of brain myeloid cells revealed activation of Itgal, Trem1, and Spp1 in western diet-induced obesity.Journal of neuroinflammation · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCentral nervous system tuberculosis (CNS-TB) may be fatal even with treatment. Neutrophils are the key mediators of TB immunopathology, and raised CSF matrix metalloproteinase-9 (MMP-9) which correlates to neutrophil count in CNS-TB is associated with neurological deficit and death. The mechanisms by which neutrophils drive TB-associated CNS matrix destruction are not clearly defined.
methodsHuman brain biopsies with histologically proven CNS-TB were stained for neutrophils, neutrophil elastase, and MMP-9. Neutrophil MMP-9 secretion and gene expression were analyzed using Luminex and real-time PCR. Type IV collagen degradation was evaluated using confocal microscopy and quantitative fluorescent assays. Intracellular signaling pathways were investigated by immunoblotting and chemical inhibitors.
resultsMMP-9-expressing neutrophils were present in tuberculous granulomas in CNS-TB and neutrophil-derived MMP-9 secretion was upregulated by Mycobacterium tuberculosis (M.tb). Concurrent direct stimulation by M.tb and activation via monocyte-dependent networks had an additive effect on neutrophil MMP-9 secretion. Destruction of type IV collagen, a key component of the blood-brain barrier, was inhibited by neutralizing neutrophil MMP-9. Monocyte-neutrophil networks driving MMP-9 secretion in TB were regulated by MAP-kinase and Akt-PI
conclusionsMultiple signaling paths regulate neutrophil-derived MMP-9 secretion, which is increased in CNS-TB. These paths may be better targets for host-directed therapies than steroids currently used in CNS-TB.
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