Transcriptome Profile of the Vascular Endothelial Cell Response to Candida albicans
1Department of Clinical Pharmacy, College of Pharmacy, and 2Department of Pharmaceutical Sciences, College of Pharmacy, and Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, 3Children’s Foundation Research Center, Le Bonheur Children’s Medical Center, 4Division of Bioinformatics, College of Arts and Sciences, University of Memphis, Tennessee; 5St. John’s Cardiovascular Research Center, Division of Infectious Diseases, Department of Medicine, Los Angeles Biomedical Research Institute at Harbor–University of California, Los Angeles (UCLA), Medical Center, Torrance, 6The David Geffen School of Medicine at UCLA, Los Angeles, California
Background.
During hematogenously disseminated candidiasis, bloodborne Candida albicans interacts with vascular endothelial cells (ECs), which have the capacity to influence the local inflammatory response to this organism.
Methods.To elucidate the EC response to C. albicans, we determined the transcriptional profile of ECs infected with wild‐type C. albicans strain SC5314 and a hypovirulent cph1Δ/cph1Δ efg1Δ/efg1Δ mutant, CAN34. These EC responses were also compared to our previously published data on the response of the macrophage‐like THP‐1 cell line to C. albicans.
Results.Infection with strain SC5314 induced upregulation of EC genes involved in chemotaxis, stress response, angiogenesis, and inhibition of apoptosis. Infection with CAN34 induced weaker expression of fewer genes. The angiogenic and anti‐apoptotic response of ECs to C. albicans did not occur in THP‐1 cells. However, there was upregulation of CCL3 and CCL4 expression in both cell types. Because CCR5 is the receptor for CCL3 and CCL4, we tested the susceptibility of CCR5−/− mice to disseminated candidiasis. The survival and renal fungal burden of the CCR5−/− mice were similar to that of wild‐type control mice.
Conclusions.ECs respond significantly differently to infection with C. albicans, compared with THP‐1 cells. CCR5 is dispensable for the host defense against disseminated candidiasis in immunocompetent mice.
Received 25 October 2007; accepted 5 February 2008; electronically published 22 May 2008.
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Potential conflicts of interest: S. G. F. has received research support from Amgen, Merck, and Pfizer, and has equity in NovaDigm Therapeutics. All other authors report no relevant conflicts.
Presented in part: 8th Meeting on Candida and Candidiasis, Denver, Colorado, 13–17 March 2006 (abstract S4:3).
Financial support: National Institutes of Health (grants R01AI054928 to S.G.F., R01AI019990 to S.G.F., R01AI058145 to P.D.R., and MO1RR00425 to S.G.F.); Toyota USA (donation of the Olympus phase‐contrast microscope used for these studies).
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K. S. B. and H. P. contributed equally to this work.