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Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice

Macrophage–Leishmania interactions are central to parasite growth and disease outcome. Macrophages have developed various strategies to fight invaders, including oxidative burst. While some microorganisms seem to survive and even thrive in an oxidative environment, others are susceptible and get kil...

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Autores principales: Bichiou, Haifa, Rabhi, Sameh, Ben Hamda, Cherif, Bouabid, Cyrine, Belghith, Meriam, Piquemal, David, Trentin, Bernadette, Rabhi, Imen, Guizani-Tabbane, Lamia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554229/
https://www.ncbi.nlm.nih.gov/pubmed/34722338
http://dx.doi.org/10.3389/fcimb.2021.748738
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author Bichiou, Haifa
Rabhi, Sameh
Ben Hamda, Cherif
Bouabid, Cyrine
Belghith, Meriam
Piquemal, David
Trentin, Bernadette
Rabhi, Imen
Guizani-Tabbane, Lamia
author_facet Bichiou, Haifa
Rabhi, Sameh
Ben Hamda, Cherif
Bouabid, Cyrine
Belghith, Meriam
Piquemal, David
Trentin, Bernadette
Rabhi, Imen
Guizani-Tabbane, Lamia
author_sort Bichiou, Haifa
collection PubMed
description Macrophage–Leishmania interactions are central to parasite growth and disease outcome. Macrophages have developed various strategies to fight invaders, including oxidative burst. While some microorganisms seem to survive and even thrive in an oxidative environment, others are susceptible and get killed. To counter oxidative stress, macrophages switch the expressions of cytoprotective and detoxifying enzymes, which are downstream targets of the nuclear factor erythroid 2-related factor 2 (Nrf2), to enhance cell survival. We have explored the transcription of NRF2 and of its target genes and compared the effect of the parasite on their transcription in bone marrow-derived macrophages (BMdMs) from Leishmania-resistant and Leishmania-susceptible mice. While heme oxygenase 1 (HO-1) transcription is independent of the genetic background, the transcription of glutathione reductase (Gsr) and of cysteine/glutamate exchange transporter (Slc7a11), involved in glutathione accumulation, was differentially regulated in BMdMs from both mouse strains. We also show that, except for HO-1, known to favor the survival of the parasite, the transcription of the selected genes, including Gsr, CD36, and catalase (CAT), was actively repressed, if not at all time points at least at the later ones, by the parasite, especially in Balb/c BMdMs. Consistent with these results, we found that the silencing of NRF2 in this study increases the survival and multiplication of the parasite.
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spelling pubmed-85542292021-10-30 Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice Bichiou, Haifa Rabhi, Sameh Ben Hamda, Cherif Bouabid, Cyrine Belghith, Meriam Piquemal, David Trentin, Bernadette Rabhi, Imen Guizani-Tabbane, Lamia Front Cell Infect Microbiol Cellular and Infection Microbiology Macrophage–Leishmania interactions are central to parasite growth and disease outcome. Macrophages have developed various strategies to fight invaders, including oxidative burst. While some microorganisms seem to survive and even thrive in an oxidative environment, others are susceptible and get killed. To counter oxidative stress, macrophages switch the expressions of cytoprotective and detoxifying enzymes, which are downstream targets of the nuclear factor erythroid 2-related factor 2 (Nrf2), to enhance cell survival. We have explored the transcription of NRF2 and of its target genes and compared the effect of the parasite on their transcription in bone marrow-derived macrophages (BMdMs) from Leishmania-resistant and Leishmania-susceptible mice. While heme oxygenase 1 (HO-1) transcription is independent of the genetic background, the transcription of glutathione reductase (Gsr) and of cysteine/glutamate exchange transporter (Slc7a11), involved in glutathione accumulation, was differentially regulated in BMdMs from both mouse strains. We also show that, except for HO-1, known to favor the survival of the parasite, the transcription of the selected genes, including Gsr, CD36, and catalase (CAT), was actively repressed, if not at all time points at least at the later ones, by the parasite, especially in Balb/c BMdMs. Consistent with these results, we found that the silencing of NRF2 in this study increases the survival and multiplication of the parasite. Frontiers Media S.A. 2021-10-15 /pmc/articles/PMC8554229/ /pubmed/34722338 http://dx.doi.org/10.3389/fcimb.2021.748738 Text en Copyright © 2021 Bichiou, Rabhi, Ben Hamda, Bouabid, Belghith, Piquemal, Trentin, Rabhi and Guizani-Tabbane https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Bichiou, Haifa
Rabhi, Sameh
Ben Hamda, Cherif
Bouabid, Cyrine
Belghith, Meriam
Piquemal, David
Trentin, Bernadette
Rabhi, Imen
Guizani-Tabbane, Lamia
Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice
title Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice
title_full Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice
title_fullStr Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice
title_full_unstemmed Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice
title_short Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice
title_sort leishmania parasites differently regulate antioxidant genes in macrophages derived from resistant and susceptible mice
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554229/
https://www.ncbi.nlm.nih.gov/pubmed/34722338
http://dx.doi.org/10.3389/fcimb.2021.748738
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