Candida albicansIs Phagocytosed, Killed, and Processed for Antigen Presentation by Human Dendritic Cells

Abstract

Candida albicansis a component of the normal flora of the alimentary tract and also is found on the mucocutaneous membranes of the healthy host.Candidais the leading cause of invasive fungal disease in premature infants, diabetics, and surgical patients, and of oropharyngeal disease in AIDS patients. As the induction of cell-mediated immunity toCandidais of critical importance in host defense, we sought to determine whether human dendritic cells (DC) could phagocytose and degradeCandidaand subsequently presentCandidaantigens to T cells. Immature DC obtained by culture of human monocytes in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 phagocytosed unopsonizedCandidain a time-dependent manner, and phagocytosis was not enhanced by opsonization ofCandidain serum. Like macrophages (Mφ), DC recognizedCandidaby the mannose-fucose receptor. Upon ingestion, DC killedCandidaas efficiently as human Mφ, and fungicidal activity was not enhanced by the presence of fresh serum. Although phagocytosis ofCandidaby DC stimulated the production of superoxide anion, inhibitors of the respiratory burst (or NO production) did not inhibit killing ofCandida, even when phagocytosis was blocked by preincubation of DC with cytochalasin D. Further, although apparently only modest phagolysosomal fusion occurred upon DC phagocytosis ofCandida, killing ofCandidaunder anaerobic conditions was almost equivalent to killing under aerobic conditions. Finally, DC stimulatedCandida-specific lymphocyte proliferation in a concentration-dependent manner after phagocytosis of both viable and heat-killedCandidacells. These data suggest that, in vivo, such interactions between DC andC. albicansmay facilitate the induction of cell-mediated immunity.