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.
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 strainSC5314 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.
Authors: Mihai G Netea; Leo A B Joosten; Jos W M van der Meer; Bart-Jan Kullberg; Frank L van de Veerdonk Journal: Nat Rev Immunol Date: 2015-09-21 Impact factor: 53.106
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