EARLY SIGNAL-TRANSDUCTION INDUCED BY CANDIDA-ALBICANS IN MACROPHAGES THROUGH SHEDDING OF A GLYCOLIPID

Cell wall beta-1,2-oligomannosides are involved in Candida albicans bi nding to macrophages and in their stimulation to produce cytokines, Th e nature of signaling events occurring during initial interaction of m acrophage J774 cell line and C, albicans, together with the nature of molecules containing beta-1,2-oligomannosides released by the yeasts, was examined. Cocultivation led to a herbimycin A-sensitive production of tumor necrosis factor-cy, Immunofluorescence and Western blotting confirmed tyrosine phosphorylation and revealed an accumulation of 90- to 120-kDa phosphoproteins. Antibodies specific for beta-1,2-oligoman nosides showed that these epitopes were shed at an early stage from th e yeasts to the macrophage membrane, in association with a glycolipid previously described as C. albicans phospholipomannan, Incubation of m acrophages with purified phospholipomannan alone led to a signal trans duction pathway identical to that observed with living yeasts, AU of t hese results demonstrate that C. albicans phospholipomannan shedding i s involved in C, albicans-macrophage interaction through beta-1,2-olig omannosides.