Transcriptome profile of the vascular endothelial cell response to Candida albicans.
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 cph1Delta/cph1Delta efg1Delta/efg1Delta 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.
Barker
Katherine S
KS
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, University of Memphis, Tennessee, USA. ksbarker@utmem.edu
Park
Hyunsook
H
Phan
Quynh T
QT
Xu
Lijing
L
Homayouni
Ramin
R
Rogers
P David
PD
Filler
Scott G
SG
D000818:Animals; D002176:Candida albicans / Q000254:growth & development / Q000472:pathogenicity*; D002177:Candidiasis / Q000235:genetics; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology* / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007668:Kidney / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D019713:Receptors, CCR5 / Q000172:deficiency; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins
D018925:Chemokines; D018076:DNA, Complementary; D019713:Receptors, CCR5; D012313:RNA