Dendritic cells discriminate between yeasts and hyphae of the fungus Candida albicans: Implications for initiation of T helper cell immunity in vitroand in vivo

The fungus Candida albicans behaves as a commensal as well as a true pathog en of areas highly enriched in dendritic cells, such as skin and mucosal su rfaces. The ability of the fungus to reversibly switch between unicellular yeast to filamentous forms is thought to be important for virulence. Howeve r, whether it is the yeast or the hyphal form that is responsible for patho genicity is still a matter of debate. Here we show the interaction, and con sequences, of different forms of C. albicans with dendritic cells. Immature myeloid dendritic cells rapidly and efficiently phagocytosed both yeasts a nd hyphae of the fungus. Phagocytosis occurred through different phagocytic morphologies and receptors, resulting in phagosome formation. However, hyp hae escaped the phagosome and were found lying h-ee in the cytoplasm of the cells. In vitro, ingestion of yeasts activated dendritic cells for interle ukin (IL)-12 production and priming of T helper type 1 (Th1) cells, whereas ingestion of hyphae inhibited IL-12 and Th1 priming, and induced IL-4 prod uction. In vivo, generation of antifungal protective immunity was induced u pon injection of dendritic cells ex vivo pulsed with Candida yeasts but not hyphae. The immunization capacity of yeast-pulsed dendritic cells was lost in the absence of IL-12, whereas that of hypha-pulsed dendritic cells was gained in the absence of IL-4. These results indicate that dendritic cells fulfill the requirement of a cell uniquely capable of sensing the two forms of C. albicans in terms of type of immune responses elicited. By the discr iminative production of IL-12 and IL-4 in response to the nonvirulent and v irulent forms of the fungus, dendritic cells appear to meet the challenge o f Th priming and education in C. albicans saprophytism and infections.