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*
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, and
Division of Hematology, Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy;
Microbiology Section, Department of Experimental Medicine, University of Rome, Tor Vergata, Rome, Italy; and
Department of Microbiology, Montana State University, Bozeman, MT 59717
Immature myeloid dendritic cells (DC) phagocytose yeasts and hyphae
of the fungus Candida albicans and induce different Th
cell responses to the fungus. Ingestion of yeasts activates DC for
production of IL-12 and Th1 priming, while ingestion of hyphae induces
IL-4 production and Th2 priming. In vivo, generation of antifungal
protective immunity is induced upon injection of DC ex vivo pulsed with
Candida yeasts but not hyphae. In the present study we
sought to determine the functional activity of DC transfected with
yeast or hyphal RNA. It was found that DC, from either spleens or bone
marrow, transfected with yeast, but not hyphal, RNA 1) express fungal
mannoproteins on their surface; 2) undergo functional maturation, as
revealed by the up-regulated expression of MHC class II Ags and
costimulatory molecules; 3) produce IL-12 but no IL-4; 4) are capable
of inducing Th1-dependent antifungal resistance when delivered s.c. in
vivo in nontransplanted mice; and 5) provide protection against the
fungus in allogeneic bone marrow-transplanted mice, by accelerating the
functional recovery of Candida-specific
IFN-
-producing CD4+ donor lymphocytes. These results
indicate the efficacy of DC pulsed with Candida yeasts
or yeast RNA as fungal vaccines and point to the potential use of
RNA-transfected DC as anti-infective vaccines in conditions that
negate the use of attenuated microorganisms or in the case of poor
availability of protective Ags.
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