Metabolic adaptation to tissue iron overload confers tolerance to malaria

dc.creatorGozzelino, Raffaella
dc.creatorAndrade, Bruno de Bezerril
dc.creatorLarsen, Rasmus
dc.creatorLuz, Nívea Farias
dc.creatorVanoaica, Liviu
dc.creatorSeixas, Elsa
dc.creatorCoutinho, Antonio
dc.creatorCardoso, Silvia Andrade
dc.creatorRebelo, Sofia
dc.creatorPoli, Maura
dc.creatorBarral Netto, Manoel
dc.creatorDarshan, Deepak
dc.creatorKühn, Lukas C.
dc.creatorSoares, Miguel P.
dc.date2014-02-21T17:40:23Z
dc.date2014-02-21T17:40:23Z
dc.date2012
dc.date.accessioned2023-09-26T20:07:51Z
dc.date.available2023-09-26T20:07:51Z
dc.identifierGOZZELINO, R. et al. Metabolic adaptation to tissue iron overload confers tolerance to malaria. Cell Host & Microbe, v. 12, p. 696-704, 2012.
dc.identifier1934-6069
dc.identifierorg/10.1016/j.chom.2012.10.011
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/7347
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8849244
dc.descriptionDisease 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherCell Press
dc.rightsopen access
dc.subjectApoferritinas/metabolismo
dc.subjectFerritinas/metabolismo
dc.subjectSobrecarga de Ferro/metabolismo
dc.subjectMalária/metabolismo
dc.subjectMalária/parasitologia
dc.subjectPlasmodium chabaudi/imunologia
dc.subjectPlasmodium chabaudi/fisiologia
dc.subjectAnimais
dc.subjectAntioxidantes/metabolismo
dc.subjectCélulas Cultivadas
dc.subjectCeruloplasmina/metabolismo
dc.subjectCitoproteção
dc.subjectAtivação Enzimática
dc.subjectHepatócitos/metabolismo
dc.subjectInterações Hospedeiro-Parasita
dc.subjectFerro
dc.subjectFerro/metabolismo
dc.subjectProteínas Quinases JNK Ativadas por Mitógeno/metabolismo
dc.subjectCamundongos
dc.subjectCamundongos Endogâmicos C57BL
dc.subjectPlasmodium berghei/fisiologia
dc.subjectPlasmodium vivax/fisiologia
dc.titleMetabolic adaptation to tissue iron overload confers tolerance to malaria
dc.typeArticle


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