2. Academic Validation
  3. Hypothyroidism confers tolerance to cerebral malaria

Hypothyroidism confers tolerance to cerebral malaria

  • Sci Adv. 2022 Apr 8;8(14):eabj7110. doi: 10.1126/sciadv.abj7110.
Diego Rodriguez-Muñoz 1,  Ángela Sánchez 1,  Susana Pérez-Benavente 2,  Constanza Contreras-Jurado 3 4,  Ana Montero-Pedrazuela 3,  Marta Toledo-Castillo 1,  María Gutiérrez-Hernández 1,  Raquel Rodrigues-Díez 5 6,  Cintia Folgueira 7,  Ana M Briones 5 6,  Guadalupe Sabio 7,  Ignacio Monedero-Cobeta 8,  Irene Chaves-Coira 9,  David Castejón 10,  Encarnación Fernández-Valle 10,  Javier Regadera 9,  José M Bautista 2,  Ana Aranda 3 11 12,  Susana Alemany 1 11
Affiliations

Affiliations

  • 1 Departament of Metabolism and Cell Signaling, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
  • 2 Department of Biochemistry and Molecular Biology, Research Institute Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, Spain.
  • 3 Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
  • 4 Departamento de Bioquímica, Facultad de Medicina, Universidad Alfonso X El Sabio, Villanueva de la Cañada, Madrid, Spain.
  • 5 Departament of Pharmacology, Instituto de Investigación Hospital La Paz, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
  • 6 CIBER de Enfermedades Cardiovasculares, ISCIII, Madrid, Spain.
  • 7 Departament of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares, ISCIII, 28029 Madrid, Spain.
  • 8 Department of Physiology, Universidad Autónoma de Madrid, Madrid, Spain.
  • 9 Department of Anatomy, Histology and Neuroscience, Universidad Autónoma de Madrid, Madrid, Spain.
  • 10 MNR Unit (CAI de Bioimagen), Universidad Complutense de Madrid, Madrid, Spain.
  • 11 Biomedicine Unit (Unidad Asociada al CSIC), Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain.
  • 12 Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), ISCIII, Madrid, Spain.
PMID: 35385300 DOI: 10.1126/sciadv.abj7110
Abstract

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.

Figures
Products