The antioxidant response favors Leishmania parasites survival, limits inflammation and reprograms the host cell metabolism.
The oxidative burst generated by the host immune system can restrict intracellular parasite entry and growth. While this burst leads to the induction of antioxidative enzymes, the molecular mechanisms and the consequences of this counter-response on the life of intracellular human parasites are larg...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009422 |
| _version_ | 1818581309324263424 |
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| author | Marta Reverte Remzi Onur Eren Baijayanti Jha Chantal Desponds Tiia Snäkä Florence Prevel Nathalie Isorce Lon-Fye Lye Katherine L Owens Ulisses Gazos Lopes Stephen M Beverley Nicolas Fasel |
| author_facet | Marta Reverte Remzi Onur Eren Baijayanti Jha Chantal Desponds Tiia Snäkä Florence Prevel Nathalie Isorce Lon-Fye Lye Katherine L Owens Ulisses Gazos Lopes Stephen M Beverley Nicolas Fasel |
| author_sort | Marta Reverte |
| collection | DOAJ |
| description | The oxidative burst generated by the host immune system can restrict intracellular parasite entry and growth. While this burst leads to the induction of antioxidative enzymes, the molecular mechanisms and the consequences of this counter-response on the life of intracellular human parasites are largely unknown. The transcription factor NF-E2-related factor (NRF2) could be a key mediator of antioxidant signaling during infection due to the entry of parasites. Here, we showed that NRF2 was strongly upregulated in infection with the human Leishmania protozoan parasites, its activation was dependent on a NADPH oxidase 2 (NOX2) and SRC family of protein tyrosine kinases (SFKs) signaling pathway and it reprogrammed host cell metabolism. In inflammatory leishmaniasis caused by a viral endosymbiont inducing TNF-α in chronic leishmaniasis, NRF2 activation promoted parasite persistence but limited TNF-α production and tissue destruction. These data provided evidence of the dual role of NRF2 in protecting both the invading pathogen from reactive oxygen species and the host from an excess of the TNF-α destructive pro-inflammatory cytokine. |
| first_indexed | 2024-12-16T07:31:26Z |
| format | Article |
| id | doaj.art-0afbb9684d2240dd949e1accd28bc3af |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T07:31:26Z |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-0afbb9684d2240dd949e1accd28bc3af2022-12-21T22:39:20ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-03-01173e100942210.1371/journal.ppat.1009422The antioxidant response favors Leishmania parasites survival, limits inflammation and reprograms the host cell metabolism.Marta ReverteRemzi Onur ErenBaijayanti JhaChantal DespondsTiia SnäkäFlorence PrevelNathalie IsorceLon-Fye LyeKatherine L OwensUlisses Gazos LopesStephen M BeverleyNicolas FaselThe oxidative burst generated by the host immune system can restrict intracellular parasite entry and growth. While this burst leads to the induction of antioxidative enzymes, the molecular mechanisms and the consequences of this counter-response on the life of intracellular human parasites are largely unknown. The transcription factor NF-E2-related factor (NRF2) could be a key mediator of antioxidant signaling during infection due to the entry of parasites. Here, we showed that NRF2 was strongly upregulated in infection with the human Leishmania protozoan parasites, its activation was dependent on a NADPH oxidase 2 (NOX2) and SRC family of protein tyrosine kinases (SFKs) signaling pathway and it reprogrammed host cell metabolism. In inflammatory leishmaniasis caused by a viral endosymbiont inducing TNF-α in chronic leishmaniasis, NRF2 activation promoted parasite persistence but limited TNF-α production and tissue destruction. These data provided evidence of the dual role of NRF2 in protecting both the invading pathogen from reactive oxygen species and the host from an excess of the TNF-α destructive pro-inflammatory cytokine.https://doi.org/10.1371/journal.ppat.1009422 |
| spellingShingle | Marta Reverte Remzi Onur Eren Baijayanti Jha Chantal Desponds Tiia Snäkä Florence Prevel Nathalie Isorce Lon-Fye Lye Katherine L Owens Ulisses Gazos Lopes Stephen M Beverley Nicolas Fasel The antioxidant response favors Leishmania parasites survival, limits inflammation and reprograms the host cell metabolism. PLoS Pathogens |
| title | The antioxidant response favors Leishmania parasites survival, limits inflammation and reprograms the host cell metabolism. |
| title_full | The antioxidant response favors Leishmania parasites survival, limits inflammation and reprograms the host cell metabolism. |
| title_fullStr | The antioxidant response favors Leishmania parasites survival, limits inflammation and reprograms the host cell metabolism. |
| title_full_unstemmed | The antioxidant response favors Leishmania parasites survival, limits inflammation and reprograms the host cell metabolism. |
| title_short | The antioxidant response favors Leishmania parasites survival, limits inflammation and reprograms the host cell metabolism. |
| title_sort | antioxidant response favors leishmania parasites survival limits inflammation and reprograms the host cell metabolism |
| url | https://doi.org/10.1371/journal.ppat.1009422 |
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