| Autor: |
Clément Blot, Mathilde Lavernhe, Geanncarlo Lugo-Villarino, Kimberley Coulson, Marie Salon, Margot Tertrais, Rémi Planès, Karin Santoni, Hélène Authier, Godefroy Jacquemin, Mouna Rahabi, Mélissa Parny, Isabelle Raymond Letron, Etienne Meunier, Lise Lefèvre, Agnès Coste |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 43, Iss 9, Pp 114720- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114720 |
| Popis: |
Summary: Macrophages are major host cells for the protozoan Leishmania parasite. Depending on their activation state, they either contribute to the detection and elimination of Leishmania spp. or promote parasite resilience. Here, we report that the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages plays a pivotal role in the progression of Leishmania infantum infection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of the NOX2/reactive oxygen species (ROS) axis in early Nrf2 activation and, subsequently, prostaglandin E2 (PGE2)/EP2r signaling in the sustenance of Nrf2 activation upon infection. Moreover, we establish a ferroptosis-like process within macrophages as a cell death program of L. infantum and the protective effect of Nrf2 in macrophages against L. infantum death. Altogether, these results identify Nrf2 as a critical factor for the susceptibility of L. infantum infection, highlighting Nrf2 as a promising pharmacological target for the development of therapeutic approaches for the treatment of visceral leishmaniasis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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