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

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