GeneExpression in HL60 Granulocytoids and Human PolymorphonuclearLeukocytes Exposed toCandidaalbicans†

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Abstract
Candida albicansis an opportunistic human pathogen causing both superficial and disseminated diseases. It is a dimorphic fungus, switching between yeast and hyphal forms, depending on cues from its microenvironment. Hyphae play an important role in the pathogenesis of candidiasis. The host's response toCandidainfection is multifaceted and includes the participation of granulocytes as key effector cells. The aim of this investigation was to study host gene expression during granulocyte-Candidainteraction. Effector cells were generated by the granulocytic differentiation of HL60 cells. The resulting cell population was shown to be morphologically and functionally equivalent to granulocytes and is therefore referred to as HL60 granulocytoids for the purposes of this study. Gene expression profiles were determined 1 h after hosts were infected withC. albicans.ThreeCandida-granulocytoid ratios were chosen to reflect different degrees of HL60 granulocytoid inhibition ofC. albicans. The data demonstrate that at the high pathogen-host ratio,C. albicansmodulated the HL60 granulocytoid's response by downregulating the expression of known antimicrobial genes. In addition, looking at the expression of a large number of genes, not all of which have necessarily been implicated in candidastatic or candidacidal mechanisms, it has been possible to describe the physiological response of the HL60 granulocytoid to an infectious challenge withC. albicans. Finally, some of the observed changes in HL60 granulocytoid gene expression were investigated in freshly isolated human polymorphonuclear leukocytes infected withC. albicans. Similar changes were seen in these primary human cells, lending support to the validity of this model.