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Title

Effect of transgenic Leishmania major expressing mLLO-Bax-Smac fusion gene in the apoptosis of the infected macrophages

Year: 1400
COI: JR_IJBMS-24-12_007
Language: EnglishView: 80
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Authors

Maryam Aghaei - Skin Diseases and Leishmaniasis Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
Hossein Khanahmad - Department of Genetics and molecular biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Akram Jalali - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Shahrzad Aghaei - Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
Manizheh Narimani - Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Sayed Mohsen Hosseini - Department of Biostatistics & Epidemiology, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran
Fatemeh Namdar - Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Hossein Hejazi - Skin Diseases and Leishmaniasis Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract:

Objective(s): Leishmaniasis is a complex infection against which no confirmed vaccine has been reported so far. Transgenic expression of proteins involved in macrophage apoptosis-like BAX through the parasite itself accelerates infected macrophage apoptosis and prevents Leishmania differentiation. So, in the present research, the impact of the transgenic Leishmania major including mLLO-BAX-SMAC proapoptotic proteins was assayed in macrophage apoptosis acceleration. Materials and Methods: The coding sequence mLLO-Bax-Smac was designed and integrated into the pLexyNeo۲ plasmid. The designed sequence was inserted under the ۱۸srRNA locus into the L. major genome using homologous recombination. Then, mLLO-BAX-SMAC expression was studied using the Western blot, and the transgenic parasite pathogenesis was investigated compared with wild-type L. major in vitro and also in vivo. Results: Western blot and PCR results approved mLLO-BAX-SMAC expression and proper integration of the mLLO-Bax-Smac fragment under the ۱۸srRNA locus of L. major, respectively. The flow cytometry results revealed faster apoptosis of transgenic Leishmania-infected macrophages compared with wild-type parasite-infected macrophages. Also, the mild lesion with the less parasitic burden of the spleen was observed only in transgenic Leishmania-infected mice. The delayed progression of leishmaniasis was obtained in transgenic strain-injected mice after challenging with wild-type Leishmania. Conclusion: This study recommended transgenic L. major including mLLO-BAX-SMAC construct as a pilot model for providing a protective vaccine against leishmaniasis. 

Keywords:

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This Paper COI Code is JR_IJBMS-24-12_007. Also You can use the following address to link to this article. This link is permanent and is used as an article registration confirmation in the Civilica reference:

https://civilica.com/doc/1346647/

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Aghaei, Maryam and Khanahmad, Hossein and Jalali, Akram and Aghaei, Shahrzad and Narimani, Manizheh and Hosseini, Sayed Mohsen and Namdar, Fatemeh and Hejazi, Hossein,1400,Effect of transgenic Leishmania major expressing mLLO-Bax-Smac fusion gene in the apoptosis of the infected macrophages,https://civilica.com/doc/1346647

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