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Título: | Hypothyroidism confers tolerance to cerebral malaria |
Autor: | Rodriguez-Muñoz, Diego CSIC ORCID; Sánchez, Ángela CSIC ORCID; Pérez-Benavente, Susana; Contreras-Jurado, Constanza CSIC ORCID; Montero-Pedrazuela, Ana CSIC ORCID ; Toledo-Castillo, Marta; Gutiérrez-Hernández, María CSIC ORCID; Rodrigues-Díez, Raquel; Folgueira, Cintia; Briones, Ana M.; Sabio, Guadalupe CSIC ORCID; Monedero-Cobeta, Ignacio; Chaves-Coira, Irene; Castejón, David; Fernández-Valle, Encarnación; Regadera, Javier; Bautista, José M.; Aranda, Ana CSIC ORCID ; Alemany, Susana CSIC ORCID | Fecha de publicación: | 2022 | Editor: | American Association for the Advancement of Science | Citación: | Science Advances 8(14): eabj7110 (2022) | Resumen: | The modulation of the host’s metabolism to protect tissue from damage induces tolerance to infections increasing survival. Here, we examined the role of the thyroid hormones, key metabolic regulators, in the outcome of malaria. Hypothyroidism confers protection to experimental cerebral malaria by a disease tolerance mechanism. Hypothyroid mice display increased survival after infection with Plasmodium berghei ANKA, diminishing intracranial pressure and brain damage, without altering pathogen burden, blood-brain barrier disruption, or immune cell infiltration. This protection is reversed by treatment with a Sirtuin 1 inhibitor, while treatment of euthyroid mice with a Sirtuin 1 activator induces tolerance and reduces intracranial pressure and lethality. This indicates that thyroid hormones and Sirtuin 1 are previously unknown targets for cerebral malaria treatment, a major killer of children in endemic malaria areas. | Versión del editor: | http://dx.doi.org/10.1126/sciadv.abj7110 | URI: | http://hdl.handle.net/10261/283870 | DOI: | 10.1126/sciadv.abj7110 | Identificadores: | doi: 10.1126/sciadv.abj7110 e-issn: 2375-2548 |
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