Dendritic cells pulsed with fungal RNA induce protective immunity to Candida albicans in hematopoietic transplantation.
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-gamma-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.
Bacci
Angela
A
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Montagnoli
Claudia
C
Perruccio
Katia
K
Bozza
Silvia
S
Gaziano
Roberta
R
Pitzurra
Lucia
L
Velardi
Andrea
A
d'Ostiani
Cristiana Fe'
CF
Cutler
Jim E
JE
Romani
Luigina
L
D019264:Adoptive Transfer; D000818:Animals; D000946:Antigens, Fungal / Q000096:biosynthesis; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods; D002176:Candida albicans / Q000235:genetics / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000637:transplantation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D007113:Immunity, Innate / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology; D014162:Transfection
D000946:Antigens, Fungal; D016207:Cytokines; D012331:RNA, Fungal