EphA2 contributes to disruption of the blood-brain barrier in cerebral malaria


Autoři: Thayer K. Darling aff001;  Patrice N. Mimche aff001;  Christian Bray aff002;  Banlanjo Umaru aff003;  Lauren M. Brady aff002;  Colleen Stone aff001;  Carole Else Eboumbou Moukoko aff003;  Thomas E. Lane aff001;  Lawrence S. Ayong aff003;  Tracey J. Lamb aff001
Působiště autorů: Department of Pathology, University of Utah, Salt Lake City, UT, United States of America aff001;  Department of Pediatric Infectious Diseases, Emory University School of Medicine, Atlanta, GA, United States of America aff002;  Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroon aff003;  Department of Biological Sciences, University of Douala, Douala, Cameroon aff004
Vyšlo v časopise: EphA2 contributes to disruption of the blood-brain barrier in cerebral malaria. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008261
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008261

Souhrn

Disruption of blood-brain barrier (BBB) function is a key feature of cerebral malaria. Increased barrier permeability occurs due to disassembly of tight and adherens junctions between endothelial cells, yet the mechanisms governing junction disassembly and vascular permeability during cerebral malaria remain poorly characterized. We found that EphA2 is a principal receptor tyrosine kinase mediating BBB breakdown during Plasmodium infection. Upregulated on brain microvascular endothelial cells in response to inflammatory cytokines, EphA2 is required for the loss of junction proteins on mouse and human brain microvascular endothelial cells. Furthermore, EphA2 is necessary for CD8+ T cell brain infiltration and subsequent BBB breakdown in a mouse model of cerebral malaria. Blocking EphA2 protects against BBB breakdown highlighting EphA2 as a potential therapeutic target for cerebral malaria.

Klíčová slova:

Cerebral malaria – Cytokines – Cytotoxic T cells – Endothelial cells – Mouse models – Parasitic diseases – Plasmodium – T cells


Zdroje

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