Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/32133
Title: A major role for ferroptosis in Mycobacterium tuberculosis-induced cell death and tissue necrosis
Authors: Amaral, Eduardo Pereira
Costa, Diego Luís
Namasivayam, Sivaranjani
Riteau, Nicolas
Kamenyeva, Olena
Mittereder, Lara
Barber, Katrin D. Mayer
Andrade, Bruno de Bezerril
Sher, Alan
Affilliation: National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA / University of Orleans. Orleans, France.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Research Technology Branch. Bethesda, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA.
National Institutes of Health Bethesda. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. MD, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / José Silveira Foundation. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Vanderbilt University School of Medicine. Division of Infectious Diseases. Department of Medicine. Nashville, TN / Universidade Salvador. Laureate University. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA.
Abstract: Necrotic cell death during Mycobacterium tuberculosis (Mtb) infection is considered host detrimental since it facilitates mycobacterial spread. Ferroptosis is a type of regulated necrosis induced by accumulation of free iron and toxic lipid peroxides. We observed that Mtb-induced macrophage necrosis is associated with reduced levels of glutathione and glutathione peroxidase-4 (Gpx4), along with increased free iron, mitochondrial superoxide, and lipid peroxidation, all of which are important hallmarks of ferroptosis. Moreover, necrotic cell death in Mtb-infected macrophage cultures was suppressed by ferrostatin-1 (Fer-1), a well-characterized ferroptosis inhibitor, as well as by iron chelation. Additional experiments in vivo revealed that pulmonary necrosis in acutely infected mice is associated with reduced Gpx4 expression as well as increased lipid peroxidation and is likewise suppressed by Fer-1 treatment. Importantly, Fer-1-treated infected animals also exhibited marked reductions in bacterial load. Together, these findings implicate ferroptosis as a major mechanism of necrosis in Mtb infection and as a target for host-directed therapy of tuberculosis.
Keywords: Mycobacterium tuberculosis
Cell death
Infection
Iron Compounds
Tuberculosis
Necrosis
Animals
Mice
keywords: Mycobacterium tuberculosis
Morte celular
Infecção
Compostos de ferro
Tuberculose
Necrose
Animais
Camundongos
Issue Date: 2019
Publisher: Rockefeller University Press
Citation: AMARAL, E. P. et al. A major role for ferroptosis in Mycobacterium tuberculosis-induced cell death and tissue necrosis. Journal of Experimental Medicine, v. 216, n. 3, p. 556–570, 2019.
DOI: 10.1084/jem.20181776
ISSN: 0022-1007
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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