Author | Gozzelino, Raffaella | |
Author | Andrade, Bruno de Bezerril | |
Author | Larsen, Rasmus | |
Author | Luz, Nívea Farias | |
Author | Vanoaica, Liviu | |
Author | Seixas, Elsa | |
Author | Coutinho, Antonio | |
Author | Cardoso, Silvia Andrade | |
Author | Rebelo, Sofia | |
Author | Poli, Maura | |
Author | Barral Netto, Manoel | |
Author | Darshan, Deepak | |
Author | Kühn, Lukas C. | |
Author | Soares, Miguel P. | |
Access date | 2014-02-21T17:40:23Z | |
Available date | 2014-02-21T17:40:23Z | |
Document date | 2012 | |
Citation | GOZZELINO, R. et al. Metabolic adaptation to tissue iron overload confers tolerance to malaria. Cell Host & Microbe, v. 12, p. 696-704, 2012. | pt_BR |
ISSN | 1934-6069 | |
ISSN | org/10.1016/j.chom.2012.10.011 | |
URI | https://www.arca.fiocruz.br/handle/icict/7347 | |
Language | eng | pt_BR |
Publisher | Cell Press | pt_BR |
Rights | open access | pt_BR |
Title | Metabolic adaptation to tissue iron overload confers tolerance to malaria | pt_BR |
Type | Article | pt_BR |
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. | pt_BR |
Affilliation | Instituto Gulbenkian de Ciência. Oeiras, Portugal | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA | pt_BR |
Affilliation | Instituto Gulbenkian de Ciência. Oeiras, Portugal | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil | pt_BR |
Affilliation | Swiss Institute for Experimental Cancer Research (ISREC). Ecole Polytechnique Fédérale de Lausanne (EPFL). Switzerland | pt_BR |
Affilliation | Instituto Gulbenkian de Ciência. Oeiras, Portugal | pt_BR |
Affilliation | Instituto Gulbenkian de Ciência. Oeiras, Portugal | pt_BR |
Affilliation | Instituto Gulbenkian de Ciência. Oeiras, Portugal | pt_BR |
Affilliation | Instituto Gulbenkian de Ciência. Oeiras, Portugal | pt_BR |
Affilliation | University of Brescia. Dipartimento Materno Infantile e Tecnologie Biomediche. Brescia, Italy | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil | pt_BR |
Affilliation | Swiss Institute for Experimental Cancer Research (ISREC). Ecole Polytechnique Fédérale de Lausanne (EPFL). Switzerland | pt_BR |
Affilliation | Swiss Institute for Experimental Cancer Research (ISREC). Ecole Polytechnique Fédérale de Lausanne (EPFL). Switzerland | pt_BR |
Affilliation | Instituto Gulbenkian de Ciência. Oeiras, Portugal | pt_BR |
DeCS | Apoferritinas/metabolismo | pt_BR |
DeCS | Ferritinas/metabolismo | pt_BR |
DeCS | Sobrecarga de Ferro/metabolismo | pt_BR |
DeCS | Malária/metabolismo | pt_BR |
DeCS | Malária/parasitologia | pt_BR |
DeCS | Plasmodium chabaudi/imunologia | pt_BR |
DeCS | Plasmodium chabaudi/fisiologia | pt_BR |
DeCS | Animais | pt_BR |
DeCS | Antioxidantes/metabolismo | pt_BR |
DeCS | Células Cultivadas | pt_BR |
DeCS | Ceruloplasmina/metabolismo | pt_BR |
DeCS | Citoproteção | pt_BR |
DeCS | Ativação Enzimática | pt_BR |
DeCS | Hepatócitos/metabolismo | pt_BR |
DeCS | Interações Hospedeiro-Parasita | pt_BR |
DeCS | Ferro | pt_BR |
DeCS | Ferro/metabolismo | pt_BR |
DeCS | Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo | pt_BR |
DeCS | Camundongos | pt_BR |
DeCS | Camundongos Endogâmicos C57BL | pt_BR |
DeCS | Plasmodium berghei/fisiologia | pt_BR |
DeCS | Plasmodium vivax/fisiologia | pt_BR |