Skip to main content

Advertisement

SpringerLink
Log in

Arginase/nitric oxide modifications using live non-pathogenic Leishmania tarentolae as an effective delivery system inside the mammalian macrophages

  • Original Article
  • Published:
Journal of Parasitic Diseases Aims and scope Submit manuscript

Abstract

Recombinant live delivery system based on chemokine IFN-γ-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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Arenberg DA, White ES, Burdick MD, Strom SR, Strieter RM (2001) Improved survival in tumor-bearing SCID mice treated with interferon-γ-inducible protein 10 (IP-10/CXCL10). Cancer Immunol Immunother 50(10):533–538

    Article  CAS  Google Scholar 

  • Barani S, Turki H, Shafiei R, Jafarzadeh F, Maleki HH, Raeghi S (2020) Clinico-Hematological Findings of Acute Pediatric Visceral Leishmaniasis Referred to the Northeast of Iran during 2005-2015. Iranian J Parasitol 15(2):214–222

    Google Scholar 

  • Basile G, Peticca M (2009) Recombinant protein expression in Leishmania tarentolae. Mol Biotechnol 43(3):273

    Article  CAS  Google Scholar 

  • Behniafar H, Moin-Vaziri V, Mohebali M, Tabaei SJS, Zarei Z, Kazemirad E, Akhoundi B, Saharifi-Yazdi MK, Zahraei-Ramazani A (2019) Visceral leishmaniasis among children in an endemic area of northwestern Iran between 2016 and 2017: an epidemiological study. Asian Pacific J Trop Med 12(7):306

    Article  Google Scholar 

  • Bueno GCL, Koerich ATDS, Burg LB, Kretzer SL, Moral JÂGD, Pereira IA (2019) Visceral leishmaniasis mimicking systemic lupus erythematosus. Revista da Sociedade Brasileira de Medicina Tropical 52:195

    Article  Google Scholar 

  • Chaouch M, Aoun K, Ben Othman S, Ben Abid M, Ben Sghaier I, Bouratbine A, Ben Abderrazak S (2019) Development and assessment of Leishmania major and Leishmania tropica specific loop-mediated isothermal amplification assays for the diagnosis of cutaneous leishmaniasis in Tunisia. Am J Trop Med Hyg 101(1):101–107

    Article  CAS  Google Scholar 

  • Contreras-Zentella ML, Sánchez-Sevilla L, Suárez-Cuenca JA, Olguín-Martínez M, Alatriste-Contreras MG, García-García N, Orozco L, Hernández-Muñoz R (2019) The role of oxidant stress and gender in the erythrocyte arginine metabolism and ammonia management in patients with type 2 diabetes. PLoS ONE 14(7):e0219481

    Article  CAS  Google Scholar 

  • Datki Z, Olah Z, Macsai L, Pakaski M, Galik B, Mihaly G, Kalman J (2019) Application of BisANS fluorescent dye for developing a novel protein assay. PLoS ONE 14(4):e0215863

    Article  CAS  Google Scholar 

  • Genestra M, Guedes-Silva D, Souza WJS, Cysne-Finkelstein L, Soares-Bezerra RJ, Monteiro FP, Leon LL (2006a) Nitric oxide synthase (NOS) characterization in Leishmania amazonensis axenic amastigotes. Arch Med Res 37(3):328–333

    Article  CAS  Google Scholar 

  • Genestra M, Souza WJ, Guedes-Silva D, Machado GM, Cysne-Finkelstein L, Bezerra RJS, Monteiro F, Leon LL (2006b) Nitric oxide biosynthesis by Leishmania amazonensis promastigotes containing a high percentage of metacyclic forms. Arch Microbiol 185(5):348–354

    Article  CAS  Google Scholar 

  • Getaneh A, Tamrat A, Tadesse K (2015) Arginase activity in peripheral blood of patients with intestinal schistosomiasis, Wonji, Central Ethiopia. Parasite Immunol 37(7):380–383

    Article  CAS  Google Scholar 

  • Gupta G, Bhattacharjee S, Bhattacharyya S, Bhattacharya P, Adhikari A, Mukherjee A, Bhattacharyya Majumdar S, Majumdar S (2009) CXC chemokine-mediated protection against visceral Leishmaniasis: involvement of the proinflammatory response. J Infect Dis 200(8):1300–1310

    Article  CAS  Google Scholar 

  • Hasan NA, Shafiei R, Reza HG, Reza ZE, Ashok A (2020) Cytokine profile and nitric oxide levels in peritoneal macrophages of BALB/c mice exposed to Fucose-Mannose Ligand of Leishmania infantum combined with Glycyrrhizin

  • Hezari F, Niyyati M, Seyyed Tabaei SJ, Mohebali M, Moin Vaziri V, Behniafar H, Azargashb E, Taghipour N (2016) Frequency of cutaneous Leishmaniasis and species identification in suspected individuals from Golestan Province, Northern Iran in 2014. Iranian J Public Health 45(10):1348–1354

    Google Scholar 

  • Ibarra-Meneses AV, Ghosh P, Hossain F, Chowdhury R, Mondal D, Alvar J, Moreno J, Carrillo E (2017) IFN-γ, IL-2, IP-10, and MIG as biomarkers of exposure to Leishmania spp., and of cure in human visceral Leishmaniasis. Front Cellular Infect Microbiol 7(200):10196

    Google Scholar 

  • Kang TH, Bae HC, Kim SH, Seo SH, Son SW, Choi EY, Seong SY, Kim TW (2009) Modification of dendritic cells with interferon-γ-inducible protein-10 gene to enhance vaccine potency. J Gene Med 11(10):889–898

    Article  CAS  Google Scholar 

  • Kima PE, Soong L (2013) Interferon gamma in Leishmaniasis. Front Immunol 4:156

    Article  Google Scholar 

  • Klatt S, Simpson L, Maslov DA, Konthur Z (2019) Leishmania tarentolae: taxonomic classification and its application as a promising biotechnological expression host. PLoS Negl Trop Dis 13(7):e0007424

    Article  CAS  Google Scholar 

  • Ko EM, Ma JH, Guo F, Miers L, Lee E, Bannerman P, Burns T, Ko D, Sohn J, Soulika AM (2014) Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model. J Neuroinflammation 11(1):105

    Article  Google Scholar 

  • Krassner SM, Flory B (1971) Essential amino acids in the culture of Leishmania tarentolae. J Parasitol 15:917–920

    Article  Google Scholar 

  • Krathwohl MD, Anderson JL (2006) Chemokine CXCL10 (IP-10) is sufficient to trigger an immune response to injected antigens in a mouse model. Vaccine 24(15):2987–2993

    Article  CAS  Google Scholar 

  • Liu D, Uzonna JE (2012) The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response. Front Cellular Infection Microbiol 2:83

    Google Scholar 

  • Maritati M, Trentini A, Michel G, Bellini T, Almugadam S, Hanau S, Govoni M, Marty P, Contini C (2018) Subclinical Leishmania infection in patients with rheumatic diseases under biological drugs. Infection 46(6):801–809

    Article  Google Scholar 

  • Masoori L, Kheirandish F, Haghighi A, Mohebali M, Akhoundi B, Taghipour N, Gachkar L, Chegeni-Sharafi A, Moin-Vaziri V (2018) Molecular-based detection of Leishmania infantum in human blood samples in a new focus of visceral Leishmaniasis in Lorestan Province, Iran. J Arthropod-Borne Dis 12(1):67

    PubMed  PubMed Central  Google Scholar 

  • Montakhab-Yeganeh H, Abdossamadi Z, Zahedifard F, Taslimi Y, Badirzadeh A, Saljoughian N, Taheri T, Taghikhani M, Rafati S (2017) Leishmania tarentolae expressing CXCL-10 as an efficient immunotherapy approach against Leishmania major-infected BALB/c mice. Parasite Immunol 39(10):e12461

    Article  Google Scholar 

  • Morales MA, Pescher P, Späth GF (2010) Leishmania major MPK7 protein kinase activity inhibits intracellular growth of the pathogenic amastigote stage. Eukaryot Cell 9(1):22–30

    Article  CAS  Google Scholar 

  • Moreira RRD, Santos AGD, Carvalho FA, Perego CH, Crevelin EJ, Crotti AEM, Cogo J, Cardoso MLC, Nakamura CV (2019) Antileishmanial activity of Melampodium divaricatum and Casearia sylvestris essential oils on Leishmania amazonensis. Revista do Instituto de Medicina Tropical de São Paulo 61:288

    Article  Google Scholar 

  • Ng KP, Manjeri A, Lee LM, Chan ZE, Tan CY, Tan QD, Majeed AQ, Lee KL, Chuah C, Suda T, Ong ST (2018) The arginase inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) induces apoptosis in leukemic cells specifically under hypoxic conditions but CRISPR/Cas9 excludes arginase 2 (ARG2) as the functional target. PLoS ONE 13(10):e0205254

    Article  Google Scholar 

  • Oliaee RT, Sharifi I, Afgar A, Jafarzadeh A, Kareshk AT, Bamorovat M, Sharifi H, Babaei Z, Keyhani A, Keyhani A, Abedi L, Sharifi F (2019) Differential expression of TLRs 2, 4, 9, iNOS and TNF-α and arginase activity in peripheral blood monocytes from glucantime unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis caused by Leishmania tropica. Microb Pathog 126:368–378

    Article  CAS  Google Scholar 

  • Pawar H, Puri M, Fischer Weinberger R, Madhubala R, Zilberstein D (2019) The arginine sensing and transport binding sites are distinct in the human pathogen Leishmania. PLoS Neglected Trop Dis 13(4):e0007304

    Article  Google Scholar 

  • Pereira MA, Alexandre-Pires G, Câmara M, Santos M, Martins C, Rodrigues A, Adriana J, Passero LFD, Pereira da Fonseca I, Santos-Gomes G (2019) Canine neutrophils cooperate with macrophages in the early stages of Leishmania infantum in vitro infection. Parasite Immunol 41(4):e12617

    Article  CAS  Google Scholar 

  • Shafiei R, Ahmadabad Hasan N, Nezafat Firizi M, BakhshiJoibari F, Ghahremani A, Hatam GR, Ghatee MA (2019) Cytokine profile and nitric oxide levels in macrophages exposed to Leishmania infantum FML. Exp Parasitol 203:1–7

    Article  Google Scholar 

  • Silva JMD, Silva HALD, Zelenski C, Souza JADM, Hueb M, Damazo AS (2019) Analysis of macrophage subtypes and annexin A1 expression in lesions of patients with cutaneous leishmaniasis. Revista da Sociedade Brasileira de Medicina Tropical 52:909

    Google Scholar 

  • Sosa N, Pascale JM, Jiménez AI, Norwood JA, Kreishman-Detrick M, Weina PJ, Lawrence K, McCarthy WF, Adams RC, Scott C, Ransom J, Tang D, Grogl M (2019) Topical paromomycin for New World cutaneous leishmaniasis. PLoS Neglected Trop Dis 13(5):e0007253

    Article  CAS  Google Scholar 

  • Taslimi Y, Zahedifard F, Habibzadeh S, Taheri T, Abbaspour H, Sadeghipour A, Mohit E, Rafati S (2016) Antitumor effect of IP-10 by using two different approaches: live delivery system and gene therapy. J Breast Cancer 19(1):34–44

    Article  Google Scholar 

  • Toepp AJ, Bennett C, Scott B, Senesac R, Oleson JJ, Petersen CA (2019) Maternal Leishmania infantum infection status has significant impact on leishmaniasis in offspring. PLoS Neglected Trop Dis 13(2):e0007058

    Article  Google Scholar 

  • Vasquez RE, Soong L (2006) CXCL10/gamma interferon-inducible protein 10-mediated protection against Leishmania amazonensis infection in mice. Infect Immun 74(12):6769–6777

    Article  CAS  Google Scholar 

  • Wanasen N, Soong L (2008) L-arginine metabolism and its impact on host immunity against Leishmania infection. Immunol Res 41(1):15–25

    Article  CAS  Google Scholar 

  • Yao C, Chen Y, Sudan B, Donelson JE, Wilson ME (2008) Leishmania chagasi: homogenous metacyclic promastigotes isolated by buoyant density are highly virulent in a mouse model. Exp Parasitol 118(1):129–133

    Article  CAS  Google Scholar 

  • Yue L, Yan M, Tremblay ML, Lin T-J, Li H, Yang T, Song X, Xie T, Xie Z (2019) PTP1B negatively regulates nitric oxide-mediated Pseudomonas aeruginosa killing by neutrophils. PLoS ONE 14(9):e0222753

    Article  CAS  Google Scholar 

Download references

Funding

This study was funded by the grant from the Hormozgan University of Medical Sciences, Bandar Abbas, Iran (Grant No. 980288) to Dr. Hossein Montakhab-Yeganeh. The funder had no role in study design and interpretation of the current work.

Author information

Authors and Affiliations

  1. Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Alireza Badirzadeh

  2. Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

    Hossein Montakhab-Yeganeh

  3. Department of Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

    Hossein Montakhab-Yeganeh

  4. Department of Medical Laboratory Sciences, Faculty of Paramedicine, Urmia University of Medical Sciences, Urmia, Iran

    Touraj Miandoabi

Authors
  1. Alireza Badirzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hossein Montakhab-Yeganeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Touraj Miandoabi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hossein Montakhab-Yeganeh.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Badirzadeh, A., Montakhab-Yeganeh, H. & Miandoabi, T. Arginase/nitric oxide modifications using live non-pathogenic Leishmania tarentolae as an effective delivery system inside the mammalian macrophages. J Parasit Dis 45, 65–71 (2021). https://doi.org/10.1007/s12639-020-01279-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12639-020-01279-5

Keywords

Search

Navigation