Consensus Gene Network Analysis Identifies the Key Similarities and Differences in Endothelial and Epithelial Cell Dynamics after Candida albicans Infection

Abstract

Endothelial and epithelial cells are morphologically different and play a critical role in host defense during Candida albicans infection. Both cells respond to C. albicans infection by activating various signaling pathways and gene expression patterns. Their interactions with these pathogens can have beneficial and detrimental effects, and a better understanding of these interactions can help guide the development of new therapies for C. albicans infection. To identify the differences and similarities between human endothelial and oral epithelial cell transcriptomics during C. albicans infection, we performed consensus WGCNA on 32 RNA-seq samples by relating the consensus modules to endothelial-specific modules and analyzing the genes connected. This analysis resulted in the identification of 14 distinct modules. We demonstrated that the magenta module correlates significantly with C. albicans infection in each dataset. In addition, we found that the blue and cyan modules in the two datasets had opposite correlation coefficients with a C. albicans infection. However, the correlation coefficients and p-values between the two datasets were slightly different. Functional analyses of the hub of genes from endothelial cells elucidated the enrichment in TNF, AGE-RAGE, MAPK, and NF-κB signaling. On the other hand, glycolysis, pyruvate metabolism, amino acid, fructose, mannose, and vitamin B6 metabolism were enriched in epithelial cells. However, mitophagy, necroptosis, apoptotic processes, and hypoxia were enriched in both endothelial and epithelial cells. Protein–protein interaction analysis using STRING and CytoHubba revealed STAT3, SNRPE, BIRC2, and NFKB2 as endothelial hub genes, while RRS1, SURF6, HK2, and LDHA genes were identified in epithelial cells. Understanding these similarities and differences may provide new insights into the pathogenesis of C. albicans infections and the development of new therapeutic targets and interventional strategies.

Extracellular vesicles and endothelial dysfunction in infectious diseases

“…The vesicular compartments, which are transferred to the extracellular space, contain glucuronoxylomannan (GXM), a component of the cryptococcal capsule, and important lipids such as glucosylceramide and sterols, thus modulating the extracellular environment and contributing to the pathogenesis of C. neoformans infection (Rodrigues et al, 2007). Growing evidence suggests that there are significant interactions between fungal infection and endothelial dysfunction (Le et al, 2019;Naik & Mohammed, 2023). Fungal infection can induce endothelial dysfunction by activating inflammatory pathways, triggering oxidative stress, and impairing nitric oxide production (Qin et al, 2019;Qin et al, 2022).…”

“…Growing evidence suggests that there are significant interactions between fungal infection and endothelial dysfunction (Le et al., 2019 ; Naik & Mohammed, 2023 ). Fungal infection can induce endothelial dysfunction by activating inflammatory pathways, triggering oxidative stress, and impairing nitric oxide production (Qin et al., 2019 ; Qin et al., 2022 ).…”