In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

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Abstract
Dendritic cells (DC) have been shown to phagocytose and killCryptococcus neoformansin vitro and are believed to be important for inducing protective immunity against this organism. Exposure toC. neoformansoccurs mainly by inhalation, and in this study we examined the in vivo interactions ofC. neoformanswith DC in the lung. Fluorescently labeled liveC. neoformans and heat-killedC. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeledC. neoformanshad been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice withCryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosingCryptococcusin vivo and presenting antigen toC. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.