Neutrophil-Mediated Immunopathology and Matrix Metalloproteinases in Central Nervous System - Tuberculosis.

Autor:	Poh XY; Infectious Diseases Translational Research Programme, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Loh FK; Infectious Diseases Translational Research Programme, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Friedland JS; Institute for Infection and Immunity, St George's, University of London, London, United Kingdom., Ong CWM; Infectious Diseases Translational Research Programme, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore, Singapore.; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jan 12; Vol. 12, pp. 788976. Date of Electronic Publication: 2022 Jan 12 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.788976
Abstrakt:	Tuberculosis (TB) remains one of the leading infectious killers in the world, infecting approximately a quarter of the world's population with the causative organism Mycobacterium tuberculosis ( M. tb ). Central nervous system tuberculosis (CNS-TB) is the most severe form of TB, with high mortality and residual neurological sequelae even with effective TB treatment. In CNS-TB, recruited neutrophils infiltrate into the brain to carry out its antimicrobial functions of degranulation, phagocytosis and NETosis. However, neutrophils also mediate inflammation, tissue destruction and immunopathology in the CNS. Neutrophils release key mediators including matrix metalloproteinase (MMPs) which degrade brain extracellular matrix (ECM), tumor necrosis factor (TNF)-α which may drive inflammation, reactive oxygen species (ROS) that drive cellular necrosis and neutrophil extracellular traps (NETs), interacting with platelets to form thrombi that may lead to ischemic stroke. Host-directed therapies (HDTs) targeting these key mediators are potentially exciting, but currently remain of unproven effectiveness. This article reviews the key role of neutrophils and neutrophil-derived mediators in driving CNS-TB immunopathology. Competing Interests: CO received speaking fees from Qiagen outside this work. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Poh, Loh, Friedland and Ong.)
Databáze:	MEDLINE
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