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metadata.dc.type: | Artigo de Periódico |
Title: | Metabolic adaptation to tissue iron overload Confers Tolerance to Malaria |
Other Titles: | Cell Host and Microbe |
Authors: | Gozzelino, Raffaella Andrade, Bruno Bezerril Larsen, Rasmus Luz, Nívea Farias Vanoaica, Liviu Seixa, Elsa Coutinho, Antonio Cardoso, Sílvia Denise Laranjeira Rebelo, Sofia Poli, Maura Barral-Netto, Manoel Darshan, Deepak Kühn, Lukas C. Soares, Miguel P. |
metadata.dc.creator: | Gozzelino, Raffaella Andrade, Bruno Bezerril Larsen, Rasmus Luz, Nívea Farias Vanoaica, Liviu Seixa, Elsa Coutinho, Antonio Cardoso, Sílvia Denise Laranjeira Rebelo, Sofia Poli, Maura Barral-Netto, Manoel Darshan, Deepak Kühn, Lukas C. Soares, Miguel P. |
Abstract: | Disease tolerance is a defense strategy that limits the fitness costs of infection irrespectively of pathogen burden. While restricting iron (Fe) availability to pathogens is perceived as a host defense strategy, the resulting tissue Fe overload can be cytotoxic and promote tissue damage to exacerbate disease severity. Examining this interplay during malaria, the disease caused by Plasmodium infection, we find that expression of the Fe sequestering protein ferritin H chain (FtH) in mice, and ferritin in humans, is associated with reduced tissue damage irrespectively of pathogen burden. FtH protection relies on its ferroxidase activity, which prevents labile Fe from sustaining proapoptotic c-Jun N-terminal kinase (JNK) activation. FtH expression is inhibited by JNK activation, promoting tissue Fe overload, tissue damage, and malaria severity. Mimicking FtH’s antioxidant effect or inhibiting JNK activation pharmacologically confers therapeutic tolerance to malaria in mice. Thus, FtH provides metabolic adaptation to tissue Fe overload, conferring tolerance to malaria. |
Keywords: | Malaria Plasmodium infection |
metadata.dc.rights: | Acesso Aberto |
URI: | http://repositorio.ufba.br/ri/handle/ri/16447 |
Issue Date: | 2012 |
Appears in Collections: | Artigo Publicado em Periódico (Faculdade de Medicina) |
Files in This Item:
File | Description | Size | Format | |
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Manoel Barral Netto.pdf | 1,5 MB | Adobe PDF | View/Open |
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