Abstract Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts. The life cycle of Pneumocystis species consists of a trophic stage and an ascus-like cystic stage. Our lab has published data demonstrating that cysts stimulate NF-κB translocation in alveolar macrophages, but the trophic form does not. Here, we demonstrate that infection of wild-type adult mice with a normal mixture of trophic and cystic P. murina life forms elicits a more robust innate immune response in the alveolar spaces and lung parenchyma than infection with the trophic form alone. To determine the pattern recognition receptors that bind trophozoites and cysts, we examined expression of C-type lectin receptors on lung CD11c+ dendritic cells in vivo. Infection with a mixture of trophozoites and cysts resulted in the upregulation of dectin-1 and mannose receptor, while infection with trophozoites alone resulted in upregulation of dectin-2, DEC-205 and mannose receptor. In addition, we demonstrate that bone marrow-derived dendritic cells stimulated with a mixture of trophozoites and cysts produced the proinflammatory cytokines IL-1β and IL-6. In contrast, exposure to trophozoites suppressed β-glucan-induced IL-1β, IL-6, and TNFα production by bone marrow-derived dendritic cells. A targeted gene expression assay is being used to evaluate gene expression in dendritic cells following stimulation with trophozoites alone or a mixture of trophozoites and cysts. We propose that trophozoites suppress β-glucan-signaling, but are sufficient for stimulating protective responses in immunocompetent individuals.