Abstract • 166
Opsonized candida are ingested by monocytes and monocyte-derived macrophages (MDM), but uptake of unopsonized candida is mediated only by MDM, primarily through the mannose receptor (MR). We studied the effects of Th1 cytokines, recombinant human interferon-γ (rhIFN-γ), and granulocyte-macrophage colony-stimulating factor (rhGM-CSF), and the Th2 cytokine, interleukin-4 (rhIL-4) on the uptake and killing of unopsonized C.albicans by MDM. We found that rhIFN-γ (10-1000 U/ml) and rhGM-CSF (50-500 U/ml) induced a concentration-dependent increase in the capacity of MDM to ingest and kill unopsonized C.albicans and to release O2- upon stimulation with candida. Mannan (0.1 to 5 mg/ml) or mannosylated bovine serum albumin (0.1-1.0 mg/ml) inhibited uptake of unopsonized candida by both rhIFN-γ-treated and rhGM-CSF-treated macrophages in a concentration-dependent manner, but glucan (5 mg/ml) did not. Addition of monoclonal antibodies directed against CR3 did not inhibit ingestion. These data support the concept that uptake of unopsonized candida by cytokine-activated-macrophages is mediated by the mannose receptor. Addition of recombinant human myeloperoxidase (rhMPO; concentration range, 0.8-6.4 U/ml) to rhGM-CSF-treated (200 U/ml) macrophages and unopsonized C.albicans resulted in concentration-dependent and significant increases in candida killing. rhMPO did not affect killing of candida by monocytes, nor did it affect phagocytosis of opsonized or unopsonized candida. These results indicate that exogenous rhMPO can further augment the candidacidal capacity of cytokine-activated MDM. In contrast to the effect of Th1 cytokines, a slight but insignificant increase in the extent of phagocytosis and killing of unopsonized C.albicans by MDM was achieved by the treatment of cells with 2000-5000 pg/ml rhIL-4.
