Interferon-gamma activates the oxidative killing of Candida albicans by human granulocytes

Although granulocytes are essential for the resistance against infections with Candida albicans, these cells do not kill the ingested yeast optimally. Various cytokines can enhance functional activities of granulocytes, but until now only interferon-gamma (IFN-gamma) has been applied more widely, namely in patients with chronic granulomatous disease. Since it is not certain whether IFN-gamma is able to enhance the candidacidal activity of granulocytes the present study was undertaken. Human granulocytes incubated with various concentrations of recombinant human IFN-gamma (rIFN-gamma) were studied for the phagocytosis and intracellular killing of C. albicans and their oxygen metabolism after stimulation with opsonized Candida. Results showed a small increase in the rate of phagocytosis and a dose-dependent increase of the intracellular killing of C. albicans and the production of H2O2. The increased candidacidal activity and H2O2 production by rIFN-gamma-stimulated granulocytes were inhibited by diphenylene iodonium (DPI). From these results it is concluded that the increased candidacidal activity of granulocytes activated by rIFN-gamma is caused by the increased production of reactive oxygen radicals.