Leishmania tarentolae expressing CXCL‐10 as an efficient immunotherapy approach against Leishmania major‐infected BALB/c mice

Abstract

Recent findings have demonstrated the suitability of interferon-gamma-induced protein 10 (IP-10) or CXCL-10 as an immunotherapy tool in treatment of leishmaniasis. This chemokine can overcome Leishmania (L.) infection through inducing nitric oxide (NO) production for parasite elimination. This study was undertaken to investigate the therapeutic effects of recombinant Leishmania tarentolae expressing CXCL-10 and an expression vector encoding CXCL-10 (pcDNA-CXCL-10-EGFP) in a model of BALB/c mice susceptible to infection by Leishmania major. The outcome of intervention was examined at 3 weeks post-treatment by evaluating the parameters of parasite burden (PB), arginase activity, NO and various cytokines such as IFN-γ, IL-4, IL-6 and IL-10. The results have shown that despite the efficacy of CXCL-10 expression vector as gene therapy, the live therapy strategy using L. tarentolae expressing CXCL-10 was more effective in terms of decreasing PB. Nitric oxide production increased, especially in the live therapy approaches. Arginase activity also decreased in all regimens, which demonstrates the potency of the treatment. The overall cytokine production shifted in favour of Th1 responses in the treated mice. Altogether, recombinant L. tarentolae expressing CXCL-10 represents a promising therapeutic strategy to improve treatment of cutaneous leishmaniasis.

Sambucus ebulus extract stimulates cellular responses in cutaneous leishmaniasis

“…The vital amino acid, L‐Arginine, is metabolized via iNOS or ARG based upon the important signals from the medium of macrophages. Inside these cells, immune responses through Th1 cytokines (IFN‐γ) enhance the iNOS induction and NO production, while the Th2 cytokines (IL‐4) promote the generation of ARG enzyme . Parasites clearance into macrophage cells and their survival are mediated through NO and ARG, respectively …”

“…Leishmania infection has been clinically categorized into three major forms: visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) . Globally, CL is the most prevalent form of the disease with approximately 1.2 million new cases diagnosed each year, where 90% of cases occur in seven developing countries including Afghanistan, Iran, Algeria, Peru, Brazil, Saudi Arabia and Syria …”

“…They are sustainable, economical, available and more importantly have immunomodulatory effects compared with common antileishmanial compounds . These herbal extracts can be utilized as alternative natural treatments for cancers and serious infectious diseases such as CL, in which the host immune responses are critical for evolution of the disease …”

Alternative to Chemotherapy—The Unmet Demand against Leishmaniasis

“…In addition, there was significant increase in TNF-α and IFN-γ in combinatorial therapy in comparison with single Abs ( 79 ). Abdossamadi et al and Montakhab-Yeganeh et al checked the suitability of transgenic L. tarentolae expressing leishmanial antigens such as human neutrophil peptide-1, and chemokines such as interferon-gamma-induced protein 10 or CXCL-10, respectively, as immunotherapeutic tools against L. major -infected BALB/c mice ( 80 , 81 ). Both the approaches represented a promising immunotherapeutic strategy to improve treatment of CL.…”

First case report of atypical disseminated cutaneous leishmaniasis in an opium abuser in Iran

“…Leishmaniasis, as a cosmopolitan infectious disease, is caused by protozoa parasites from the Kinetoplastida Leishmania spp., which are transmitted by the female sandfly and affects almost 12 million people worldwide 1 , 2 . The infection outcome varies according to the Leishmania species from severe cutaneous lesions to erosive mucosal ulcers with severe dermal disfigurements, to a life threatening visceral disease, depending directly on the interaction between parasites and the host immunity 3 , 4 .…”