The trophic stage of the opportunistic fungal pathogen Pneumocystis murina suppresses β-1,3-glucan-induced cytokine production, but is sufficient for generating protective CD4+ T cell and B cell responses (MPF2P.746)

Abstract

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 ascus-like cysts. 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 bone marrow-derived dendritic cells pulsed with mixed P. murina express more IL-1β and induce greater CD4+ T cell interferon-γ production than bone marrow-derived dendritic cells pulsed with the trophic form alone. Additionally, our data indicate that the trophic form suppresses β-1,3-glucan-induced IL-1β production by bone marrow-derived dendritic cells. β-1,3-glucan is the predominant structural component in the cyst wall, but is not produced by the trophic form. Despite evidence of immunosuppression, our data demonstrate that the trophic form stimulates protective CD4+ T cell and B cell responses. CD4+ T cells transferred from BALB/c donor mice infected with the trophic form alone mediate clearance in RAG2KO host mice infected with either the trophic form or mixed P. murina. Infection with the trophic form generates protective B cell responses that mediate clearance following reinfection with either trophozoites or mixed P. murina. We propose that the trophic stage suppresses β-1,3-glucan-induced cytokine production, but is sufficient for stimulating protective responses in immunocompetent individuals.