Imperial College London
Professor Robert Wilkinson

ProfessorRobertWilkinson

Faculty of Medicine, Department of Infectious Disease

Professor in Infectious Diseases
 
 
 
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Contact

 

r.j.wilkinson Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Amaral:2022:10.1084/jem.20220504,
author = {Amaral, E and Foreman, TW and Namasivayam, S and Hilligan, KL and Kauffman, K and Bomfim, CCB and Costa, D and Barreto-Duarte, B and Gurgel-Rocha, C and Santana, MF and Cordeiro-Santos, M and Du, Bruyn E and Riou, C and Aberman, K and Wilkinson, RJ and Barber, DL and Mayer-Barber, K and Andrade, BB and Sher, AF},
doi = {10.1084/jem.20220504},
journal = {Journal of Experimental Medicine},
title = {GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection},
url = {http://dx.doi.org/10.1084/jem.20220504},
volume = {219},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation–mediated cell death (ferroptosis), a process previously implicated in the necrotic pathology seen in Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, and lipid peroxidation in patients with active tuberculosis and assess the role of this pathway in mice genetically deficient in or overexpressing Gpx4. We found that Gpx4-deficient mice infected with Mtb display substantially increased lung necrosis and bacterial burdens, while transgenic mice overexpressing the enzyme show decreased bacterial loads and necrosis. Moreover, Gpx4-deficient macrophages exhibited enhanced necrosis upon Mtb infection in vitro, an outcome suppressed by the lipid peroxidation inhibitor, ferrostatin-1. These findings provide support for the role of ferroptosis in Mtb-induced necrosis and implicate the Gpx4/GSH axis as a target for host-directed therapy of tuberculosis.
AU  - Amaral,E
AU  - Foreman,TW
AU  - Namasivayam,S
AU  - Hilligan,KL
AU  - Kauffman,K
AU  - Bomfim,CCB
AU  - Costa,D
AU  - Barreto-Duarte,B
AU  - Gurgel-Rocha,C
AU  - Santana,MF
AU  - Cordeiro-Santos,M
AU  - Du,Bruyn E
AU  - Riou,C
AU  - Aberman,K
AU  - Wilkinson,RJ
AU  - Barber,DL
AU  - Mayer-Barber,K
AU  - Andrade,BB
AU  - Sher,AF
DO  - 10.1084/jem.20220504
PY  - 2022///
SN  - 0022-1007
TI  - GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection
T2  - Journal of Experimental Medicine
UR  - http://dx.doi.org/10.1084/jem.20220504
UR  - http://hdl.handle.net/10044/1/100503
VL  - 219
ER  -
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