Hypothyroidism confers tolerance to cerebral malaria

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...

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Detalles Bibliográficos
Autores: Rodriguez-Muñoz, Diego, Sánchez, Ángela, Pérez-Benavente, Susana, Contreras-Jurado, Constanza, Montero-Pedrazuela, Ana, Toledo-Castillo, Marta, Gutiérrez-Hernández, María, Rodrigues Díez, Raquel, Folgueira, Cintia, Briones Alonso, Ana María, Sabio, Guadalupe, Monedero-Cobeta, Ignacio, Chávez-Coira, Irene, Castejón, David, Fernández-Valle, Encarnación, Regadera González, Javier Fco., Bautista, José M., Aranda, Ana, Alemany, Susana
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/707605
Acceso en línea:http://hdl.handle.net/10486/707605
https://dx.doi.org/10.1126/sciadv.abj7110
Access Level:acceso abierto
Palabra clave:Malaria
Brain
Hypothyroidism
Mice
Thyroid hormones
Medicina
Descripción
Sumario: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