Luigina Romani

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-γ-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.

Romani & Puccetti reply

Replying to G. J. Maghzal . 10.1038/nature13844 (2014) After our initial observation of defective tryptophan catabolism in experimental chronic granulomatous disease (CGD)1, several laboratories have been testing the indoleamine 2,3-dioxygenase (IDO1) competence of cells from CGD patients. In most instances, they found no impairment in IDO1 competence in terms of tryptophan catabolic activity in vitro by polymorphonuclear leukocytes and monocyte-derived dendritic cells2,3, leading to the conclusion that there is no obvious defect in the production of kynurenine (the first by-product of tryptophan degradation)—hence in the IDO1-dependent mechanism of tolerogenesis as a whole in human CGD. In the accompanying Comment4, Maghzal report that tryptophan catabolism is unaffected in chronic granulomatous disease, again by measurements of kynurenine production.