Opsonization of Cryptococcus neoformans by human immunoglobulin G: role of immunoglobulin G in phagocytosis by macrophages.

The role of immunoglobulin G (IgG) as an opsonin in phagocytosis of Cryptococcus neoformans by macrophages was investigated. Labeling with 125I showed that IgG isolated from normal human serum bound to non-encapsulated C. neoformans. Furthermore, IgG-opsonized cryptococci were agglutinated by anti-serum to IgG heavy chains, indicating that normal human serum contains antibody that will bind to the yeast surface. The IgG isolated from normal serum accounted for all opsonizing activity found in normal human serum, since differences were not noted between the opsonizing activities of whole serum, heat-inactivated serum and purified IgG when these opsonins were compared at equivalent concentrations of IgG. Phagocytosis of IgG-opsonized cryptococci was inhibited by anti-macrophage IgG, a reagent known to block Fc-mediated attachment and ingestion, and by pepsin digestion of opsonizing IgG. Thus, IgG opsonization is an Fc-dependent process. Opsonizing IgG appears to play its major role during the attachment phase of phagocytosis, since antimacrophage IgG blocked attachment of cryptococci to macrophages but could not block ingestion of IgG-opsonized cryptococci that had been allowed to attach to macrophages. Ingestion of opsonized cryptococci was not blocked by 2-deoxy-D-glucose, a reagent known to block Fc-mediated ingestion, thus confirming that IgG has a primary role in attachment and suggesting that ingestion is mediated by a process that is not Fc dependent.