Global Transcriptome Profiling of Human Endothelial Cells in Response to Infection with Non-mutant Morphological Forms of <em>Candida albicans</em> — ASN Events
  1. Schedule
  2. Symposium 1 - Bacterial Triggers for Host Response; The Interplay Between Signalling Pathways
  3. Global Transcriptome Profiling of Human Endothelial Cells in Response to Infection with Non-mutant Morphological Forms of Candida albicans

Global Transcriptome Profiling of Human Endothelial Cells in Response to Infection with Non-mutant Morphological Forms of Candida albicans (#19)

Crystale SY Lim 1 2 , Yee Hock Tan 1 , Rozita Rosli 3 , Heng Fong Seow 4 , Pei Pei Chong 1
  1. Department of Biomedical Sciences, Universiti Putra Malaysia, Serdang, Malaysia
  2. Department of Biotechnology, UCSI University, Cheras, Malaysia
  3. Department of Gynecology & Obstetrics, Universiti Putra Malaysia, Serdang, Malaysia
  4. Department of Pathology, Universiti Putra Malaysia, Serdang, Malaysia

Background:

Candida albicans, the most prevalent fungal pathogen in humans, is able to switch between the yeast, pseudohyphae and hyphae forms, where this switching is regulated by quorum-sensing molecules (QSMs) such as farnesol. However, the mechanism(s) by which C. albicans cells transmigrate across the endothelial layer in systemic infections, and the host response to contact with the fungal cells in their natural morphological forms are still under investigation.

Methods:

In this in vitro study, microarray transcriptome profiling was carried out to investigate the response of human umbilical vein endothelial cells (HUVEC) to invasion by non-mutant C. albicans hyphae (1 x 106 cells/well), pseudohyphae (1 x 106 cells/well with 30 µM farnesol) and blastospores (5 x 107 cells/well). Incubation for all conditions, including the appropriate controls, was carried out for 8 hours.

Results:

Infection with blastospores induced the strongest, broadest differential gene expression from HUVEC, while the transcriptional response toward hyphae and pseudohyphae were clustered together. Differentially expressed genes were mostly involved in cell death, inflammation, immune response and chemotaxis. The presence of exogenous farnesol during C. albicans infection triggered more HUVEC response as compared to C. albicans-alone infection, while the down-regulation of CXCR4 and OPN3 during HUVEC treatment with farnesol suggests that farnesol may interfere with the G protein-receptor pathway as part of interspecies communication. XTT assays to investigate the effect of farnesol on HUVEC cytotoxicity showed that HUVEC cell death was positively correlated with farnesol concentration and alcohol content in the preparative vehicle.

Conclusions:

These results suggest that the three major morphologies of non-mutant C. albicans have different functional capabilities in host micro-environments. In addition, C. albicans QSMs such as farnesol may play important roles during invasion and transmigration by influencing C. albicans morphology and also possibly as a cytotoxic agent towards host cells.