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

Leire Aparicio-Fernandez; Aitziber Antoran; Maialen Areitio; Oier Rodriguez-Erenaga; Leire Martin-Souto; Idoia Buldain; Joana Márquez; Aitor Benedicto; Beatriz Arteta; Aize Pellon; David L Moyes; Aitor Rementeria; Andoni Ramirez-Garcia

doi:10.1016/j.micinf.2024.105305

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

Microbes Infect. 2024 Jan 29:105305. doi: 10.1016/j.micinf.2024.105305. Online ahead of print.

Affiliations

¹ Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa 48940, Spain.
² Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa 48940, Spain. Electronic address: aitziber.antoran@ehu.eus.
³ Department of Immunology, Microbiology, and Parasitology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain.
⁴ Cellular Biology and Histology Department, University of the Basque Country (UPV/EHU), Leioa 48940, Spain.
⁵ Cellular Biology and Histology Department, University of the Basque Country (UPV/EHU), Leioa 48940, Spain; Cancer and Translational Medicine Research Group, University of Basque Country (UPV/EHU), Leioa 48940, Spain.
⁶ Centre for Host-Microbiome Interactions, Fac. of Dentistry, Oral & Craniofacial Science, King's College London, London SE1 1UL, United Kingdom.

PMID: 38296157
DOI: 10.1016/j.micinf.2024.105305

Abstract

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.

Keywords: Aerobic glycolysis; Candida; Immune response; Inflammation; Liver endothelium; Metabolism.