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Fig. 2 | Parasites & Vectors

Fig. 2

From: New "light" for one-world approach toward safe and effective control of animal diseases and insect vectors from leishmaniac perspectives

Fig. 2

Diagramatic illustration depicting three different schemes of Leishmania-based photodynamic vaccination in vitro. Transgenic:alad/pbgd, Porphyrinogenic Leishmania transfected with two mammalian cDNAs encoding the 2nd and 3rd enzymes in heme biosynthetic pathway, rendering them susceptible to delta-aminolevulinate (ALA)-induced neogenesis of uroporphyrin (URO); PC, Si-phthalocyanine photosensitizer [6, 11, 12]; Light, Illumination; Blue and red lightening symbols, Blue (400–500 nm wavelength) and red (~600 nm wavelength) for excitation of URO and PC, respectively. Scheme 1: In-antigen presenting cell (APC) single PS-sensitization/photo-inactivation [22]. 1–2, Phagocytosis of porphyrinogenic, but untreated Leishmania by APC; 3, Fusion of Leishmania-containing phagosome with lysosome; 4, Leishmania differentiation into amastigotes and their replication in the phagolysosomes; 5, Exposure of the parasitized APC to ALA, resulting in porphyrinogenesis of both APC and phagolysosomal amastigotes; 6, Removal of ALA, resulting in disappearance of porphyrins from APC and persistence of URO in amastigotes; 7–8, Illumination of these APC resulting in selective lysis of URO-loaded amastigotes, releasing vaccines into phagolysosomes and cytosol. Scheme 2: Same as Scheme 1, except that porphyrinogenic Leishmania are doubly PS-sensitized with ALA and PC in the dark before use for infecting APC [35]. 1–4, as described for Scheme 1, except that the Leishmania are pre-loaded with URO and PC, hence no further ALA treatment; 5–6, Illumination of the infected cells with blue and red light to excite URO and PC, lysing amastigotes with singlet oxygen and other ROS generated for releasing vaccines in APC. Scheme 3: Same as Schemes 1–2, except that Leishmania are pre-PS-sensitized and pre-photo-inactivated before use for vaccine delivery to APC [12]. 1–4, Uptake of oxidatively photo-inactivated Leishmania by APC, lysosome-phagosome fusion and their lysis to release vaccines as described

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