Arginase/nitric oxide modifications using live non-pathogenic Leishmania tarentolae as an effective delivery system insi
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ORIGINAL ARTICLE
Arginase/nitric oxide modifications using live non-pathogenic Leishmania tarentolae as an effective delivery system inside the mammalian macrophages Alireza Badirzadeh1 • Hossein Montakhab-Yeganeh2,3 • Touraj Miandoabi4
Received: 19 August 2020 / Accepted: 18 September 2020 Ó Indian Society for Parasitology 2020
Abstract Recombinant live delivery system based on chemokine IFN-c-inducible protein-10 kDa (CXCL 10 or IP-10), as a suitable immunotherapy tool, have been used for the treatment of Leishmania infections. This chemokine can defeat Leishmania spp. infection via producing nitric oxide (NO) for parasite killing. This study was performed to investigate the effects of IP-10 on the infected human macrophages by L. tarentolae expressing IP-10. We also quantified the arginase activity and NO production in the co-cultured human macrophages with L. tarentolae expressing IP-10 as compared with wild L. tarentolae. The results elucidate that in the infected cells with L. tarentolae expression of IP-10 the arginase activity decreased, and inversely, NO production intensely increased. Altogether, L. tarentolae expressing IP-10 shows a favorable therapeutic tool to improve the treatment of Leishmania infection. This work suggests that L. tarentolae expressing IP-10 cause specific effects on the metabolic pathways of the macrophage host, which might enable the host cells in killing of parasites and decreasing the survival of them against Leishmania infection. & Hossein Montakhab-Yeganeh [email protected]; [email protected] 1
Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
2
Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
3
Department of Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
4
Department of Medical Laboratory Sciences, Faculty of Paramedicine, Urmia University of Medical Sciences, Urmia, Iran
Keywords IP-10 Arginase activity Nitic oxide Leishmania tarentolae Immunotherapy Leishmaniasis
Introduction Leishmaniasis are categorized as a neglected parasitic tropical infection, which can be caused by one of the major order of Kinetoplastida protozoan parasites, Leishmania (Silva et al. 2019). The disease is an important threat for public health in the tropical and semitropical regions of the world (Chaouch et al. 2019; Maritati et al. 2018; Masoori et al. 2018; Moreira et al. 2019). This infectious disease are reported throughout 98 countries worldwide, which is caused spectrum of manifestation including cutaneous to systemic disease (Bueno et al. 2019; Chaouch et al. 2019; Hezari et al. 2016; Sosa et al. 2019; Toepp et al. 2019). This tropical parasitic infection has several major clinical forms including cutaneous, visceral, and mucocutaneous leishmaniasis (Behniafar et al. 2019). Intermediate hosts, sand fly, and directly inject flagellated promastigotes into the tegument of hosts and
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