Resistance ofHistoplasma capsulatumto killing by human neutrophils

摘要

The basis for resistance of yeast form ofHistoplasma capsulatumto antifungal activity of human neutrophils was studied. In limiting dilution assays and short term coculture assays human neutrophils were ineffective in killingH. capsulatumwhereasCandida albicanswas readily killed. By contrast, in a cell free hydrogen peroxide-peroxidase-halide systemH. capsulatumwas as sensitive to killing asC. albicans. Moreover, lysate of human neutrophils effectively substituted for horse-radish peroxidase in a cell free system for killingH. capsulatum. H. capsulatumelicited significant products of the oxidative burst in human neutrophils as detected by luminol-enhanced chemiluminescence. However, the response was two-fold less (p<0.05) than that induced byC. albicans. Transmission electron microscopy studies showed that phagosome-lysosome fusion took place when neutrophils phagocytosedC. albicansorH. capsulatum. Taken together, these findings indicate that, even thoughH. capsulatumelicits an oxidative burst and phagosome-lysosome fusion within the phagosome, it is capable of evading damage in short term assays.