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Investigating neutrophil cell death in TB pathogenesis

Fisher, Kimone L; Rajkumar-Bhugeloo, Kerishka; Moodley, Denelle; Mpotje, Thabo; Ramsuran, Duran; Ndung'u, Thumbi; Marakalala, Mohlopheni J; (2022) Investigating neutrophil cell death in TB pathogenesis. Gates Open Research , 5 , Article 175. 10.12688/gatesopenres.13472.2. Green open access

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Abstract

BACKGROUND: Neutrophils are one of the major early role players in antimycobacterial immunity. Upon infection, neutrophils can undergo NETosis, a cell death characterized by release of neutrophil extracellular traps (NETs). The role of NETosis in TB progression remains poorly characterized. We aim to characterize mechanisms underlying NETosis during TB pathogenesis by identifying genes that drive the cell death, and to determine their potential as markers of disease progression in high-risk individuals. Finally, we intend to evaluate neutrophil associated genes as targets for host directed therapy to reduce pathological damage caused by NETosis. METHODS: Quantitative PCR will be used to quantify expression of specific genes identified in the blood of individuals with active lung disease (n=30), compared to those from healthy (n=30) and latently infected individuals (LTBI) (n=30). In addition, temporal events associated with NETosis will be measured using live microscopy in a neutrophil in vitro model of Mycobacterium tuberculosis (Mtb) infection. Candidate genes found to be associated with NETosis will be targeted with pharmaceutical inhibitors. CONCLUSION: Genes associated with neutrophil mediated cell death may serve as potential biomarkers of pathological damage and disease progression, as well as targets for host-directed therapy.

Type: Article
Title: Investigating neutrophil cell death in TB pathogenesis
Open access status: An open access version is available from UCL Discovery
DOI: 10.12688/gatesopenres.13472.2
Publisher version: https://doi.org/10.12688/gatesopenres.13472.2
Language: English
Additional information: © 2022 Fisher KL et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Neutrophils, Tuberculosis, NETosis
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10148713
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