Team:CGU Taiwan/Background
Background
Leishmania
Leishmania is a genus of trypanosomes protozoa that are responsible for leishmaniasis, a blood-borne disease spread by blood-sucking sandflies. Leishmania multiply and develop extracellularly as promastigotes in the digestive tract of the sandflies. When the female fly takes blood meals, the promastigotes are delivered into the skin of the mammalian host. They will directly infect macrophages, where they differentiate into amastigotes and multiply intracellularly as such.
Leishmania as a model organism
Leishmania are aerobic organisms that rely on oxidative phosphorylation, but are defective in the synthesis of heme which is required for electron transport respiratory complexes. The genetic deficiency of heme biosynthesis in Leishmania makes it possible to produce transgenic DT mutants, which are inducible with delta-aminolevulinate (ALA) for accumulation of uroporphyrin I (URO) as a photosensitizer (PS).
Photosensitizers like uroporphyrin and aluminum phthalocyanine (PC) can be excited when illuminated at specific wavelengths and produce singlet oxygen and reactive oxygen species (ROS) to kill these parasitic protozoa (Oxidative inactivation).We adapted a combinational approach by loading the Leishmania DT mutants both endogenously with URO via the use of ALA and exogenously with PC. After URO and PC are illuminated by specific wavelength of light, double inactivation will kill Leishmania with proven effectiveness. Therefore, photo-inactivated Leishmania may be used as a carrier for delivery of antigen proteins to the antigen-presenting cells and induce humoral and cell-mediated immunity. This photodynamic Leishmania system provides us two major advantages to produce immunologic adjuvant.
