Histoplasma capsulatum yeasts are phagocytosed via very late antigen-5, killed, and processed for antigen presentation by human dendritic cells

Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of wor ld-wide importance. As the induction of cell-mediated immunity to Hc is of critical importance in host defense, we sought to determine whether dendrit ic cells (DC) could function as a primary APC for this pathogenic fungus. D C obtained by culture of human monocytes in the presence of GM-CSF and IL-4 phagocytosed Hc yeasts in a time-dependent manner. Upon ingestion, the int racellular growth of yeasts within DC was completely inhibited compared wit h rapid growth within human macrophages. Electron microscopy of DC with ing ested Hc revealed that many of the yeasts were degraded as early as 2 h pos tingestion. In contrast to macrophages, human DC recognized Hc yeasts via t he fibronectin receptor, very late Ag-5, and not via CD18 receptors. DC sti mulated Hc-specific lymphocyte proliferation in a concentration-dependent m anner after phagocytosis of viable and heat-killed Dc yeasts, but greater p roliferation was achieved after ingestion of viable yeasts. These data demo nstrate that human DC can phagocytose and degrade a fungal pathogen and sub sequently process the appropriate Ags for stimulation of lymphocyte prolife ration. In vivo, such interactions between DC and Hc may facilitate the ind uction of cell-mediated immunity.