PMID- 34722338 OWN - NLM STAT- MEDLINE DCOM- 20211124 LR - 20211124 IS - 2235-2988 (Electronic) IS - 2235-2988 (Linking) VI - 11 DP - 2021 TI - Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice. PG - 748738 LID - 10.3389/fcimb.2021.748738 [doi] LID - 748738 AB - 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. CI - Copyright (c) 2021 Bichiou, Rabhi, Ben Hamda, Bouabid, Belghith, Piquemal, Trentin, Rabhi and Guizani-Tabbane. FAU - Bichiou, Haifa AU - Bichiou H AD - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis, Tunis-Belvedere, Tunisia. AD - Faculty of Sciences of Tunis, Universite de Tunis El Manar, Tunis, Tunisia. FAU - Rabhi, Sameh AU - Rabhi S AD - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis, Tunis-Belvedere, Tunisia. FAU - Ben Hamda, Cherif AU - Ben Hamda C AD - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis, Tunis-Belvedere, Tunisia. FAU - Bouabid, Cyrine AU - Bouabid C AD - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis, Tunis-Belvedere, Tunisia. AD - Faculty of Sciences of Tunis, Universite de Tunis El Manar, Tunis, Tunisia. FAU - Belghith, Meriam AU - Belghith M AD - Department of Immunology, Institut Pasteur de Tunis, University Tunis El-Manar, Tunis, Tunisia. FAU - Piquemal, David AU - Piquemal D AD - Acobiom, Grabels, France. FAU - Trentin, Bernadette AU - Trentin B AD - Acobiom, Grabels, France. FAU - Rabhi, Imen AU - Rabhi I AD - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis, Tunis-Belvedere, Tunisia. AD - Higher Institute of Biotechnology at Sidi-Thabet, Biotechpole Sidi-Thabet, University of Manouba, Sidi-Thabet, Tunisia. FAU - Guizani-Tabbane, Lamia AU - Guizani-Tabbane L AD - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis, Tunis-Belvedere, Tunisia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211015 PL - Switzerland TA - Front Cell Infect Microbiol JT - Frontiers in cellular and infection microbiology JID - 101585359 RN - 0 (Antioxidants) SB - IM MH - Animals MH - Antioxidants MH - *Leishmania/genetics MH - Macrophages MH - Mice MH - Mice, Inbred BALB C MH - Oxidative Stress MH - *Parasites PMC - PMC8554229 OTO - NOTNLM OT - Leishmania OT - NRF2 OT - antioxidants OT - macrophage OT - resistance OT - susceptibility COIS- 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. EDAT- 2021/11/02 06:00 MHDA- 2021/11/25 06:00 PMCR- 2021/01/01 CRDT- 2021/11/01 09:24 PHST- 2021/07/28 00:00 [received] PHST- 2021/09/20 00:00 [accepted] PHST- 2021/11/01 09:24 [entrez] PHST- 2021/11/02 06:00 [pubmed] PHST- 2021/11/25 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fcimb.2021.748738 [doi] PST - epublish SO - Front Cell Infect Microbiol. 2021 Oct 15;11:748738. doi: 10.3389/fcimb.2021.748738. eCollection 2021.