Candida albicans increases the aerobic glycolysis and activates MAPK–dependent inflammatory response of liver sinusoidal endothelial cells

The liver, and more specifically, the liver sinusoidal endothelial cells, constitute the beginning of one of the most important responses for the elimination of hematogenously disseminated Candida albicans. Therefore, we aimed to study the mechanisms involved in the interaction between these cells a...

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Detalles Bibliográficos
Autores: Aparicio Fernández, Leire, Antorán Díaz, Aitziber, Areitio Beramendi, Maialen, Rodríguez Ereñaga, Oier, Martín Souto, Leire, Buldain Garriz, Idoia, Márquez Clavijo, Joana, Benedicto García, Aitor, Arteta Ruiz, Beatriz, Pellón Rodríguez, Aize, Moyes, David L., Rementeria Ruiz, Aitor Domingo, Ramírez García, Andoni
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/68769
Acceso en línea:http://hdl.handle.net/10810/68769
Access Level:acceso abierto
Palabra clave:liver endothelium
Candida
inflammation
metabolism
immune response
aerobic glycolysis
Descripción
Sumario:The liver, and more specifically, the liver sinusoidal endothelial cells, constitute the beginning of one of the most important responses for the elimination of hematogenously disseminated Candida albicans. Therefore, we aimed to study the mechanisms involved in the interaction between these cells and C. albicans. Transcriptomics-based analysis showed an increase in the expression of genes related to the immune response (including receptors, cytokines, and adhesion molecules), as well as to aerobic glycolysis. Further in vitro analyses showed that IL-6 production in response to C. albicans is controlled by MyD88- and SYK-pathways, suggesting an involvement of Toll-like and C-type lectin receptors and the subsequent activation of the MAP-kinases and c-Fos/AP-1 transcription factor. In addition, liver sinusoidal endothelial cells undergo metabolic reprogramming towards aerobic glycolysis induced by C. albicans, as confirmed by the increased Extracellular Acidification Rate and the overexpression of enolase (Eno2), hexonikase (Hk2) and glucose transporter 1 (Slc2a1). In conclusion, these results indicate that the hepatic endothelium responds to C. albicans by increasing aerobic glycolysis and promoting an inflammatory environment.