Immunobiological effect of Candida albicans on mouse liver endothelial cells and melanoma
Ikusi/ Ireki
Data
2024-03-01Egilea
Aparicio Fernández, Leire
Laburpena
Candida albicans is an opportunistic pathogenic fungus capable of reaching the bloodstream and causing disseminated infections. This thesis aimed, firstly to clarify the mechanisms activated in liver sinusoidal endothelial cells (LSEC) by C. albicans and, secondly, to examine the effect exerted by C. albicans on tumor cells. In this regard, the results determine that C. albicans is capable of inducing an inflammatory response initiated by its recognition by Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) present in LSECs, leading to the activation of the MAPK/c-Fos pathways, mainly through ERK1/2, JNK, and p38, inducing a cytokine-mediated inflammatory response and a metabolic reprogramming that enables its energy sustenance. In relation to melanoma cells, in vitro and in vivo assays reveal that the fungus promotes adhesion to endothelial cells, migration, the generation of a pro-angiogenic environment, the Warburg effect, and metastasis in melanoma cells, favoring tumor development and progression. Although additional transcriptomic analyses and in vitro assays suggest the involvement of the MAPK/p38 pathway, further studies are required to clarify the underlying mechanisms. In summary, this work indicates that the presence of C. albicans could lead LSECs to promote a pro-inflammatory and pro-metastatic microenvironment, while melanoma cells may undergo phenotypic and metabolic changes, increasing their metastatic potential.