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      The Comparison of the IFN-ɤ, TNF-α and IL-10 Cytokines in Healing and Non-healing Cutaneous Leishmaniasis

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          Abstract

          Background:

          Leishmaniasis is one of the main vectors borne and neglected tropical parasitic diseases. T cell cytokine responses are highly important in the presentations of disease such as control or progression, and understanding of the host immunological response is valuable in diagnosis, follow-up, and vaccine designs. In the current study, the profile of IFN-ɤ, TNF-α, and IL-10 cytokines was investigated through the ELISA technique in PBMCs isolated from antimony resistance and susceptible patients.

          Methods:

          In this experimental study, 54 patients with healing (n=27) or non-healing (n=27) CL were recruited. Lesion samples were collected to determine the genotype of Leishmania spp. and peripheral blood mononuclear cells (PBMCs) were obtained to evaluate the cytokines profiles using soluble Leishmania antigen (SLA) and phytohaemagglutinin (PHA) mitogen. Cytokines were assessed by the ELISA technique

          Results:

          The IFN-ɤ and TNF-α cytokines were significantly increased in the healing group treated with both SLA antigen and PHA mitogen ( P<0.001). The level of IL-10 was significantly increased in non-healing and significantly declined in healing groups ( P<0.001).

          Conclusion:

          The profile of IFN-ɤ, TNF-α, and IL-10 cytokines are crucially associated with the response of treatment.

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          Most cited references42

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          Leishmaniasis: a review

          Leishmaniasis is caused by an intracellular parasite transmitted to humans by the bite of a sand fly. It is endemic in Asia, Africa, the Americas, and the Mediterranean region. Worldwide, 1.5 to 2 million new cases occur each year, 350 million are at risk of acquiring the disease, and leishmaniasis causes 70,000 deaths per year. Clinical features depend on the species of Leishmania involved and the immune response of the host. Manifestations range from the localized cutaneous to the visceral form with potentially fatal outcomes. Many drugs are used in its treatment, but the only effective treatment is achieved with current pentavalent antimonials.
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            A Historical Overview of the Classification, Evolution, and Dispersion of Leishmania Parasites and Sandflies

            Background The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale. Methodology and Principal Findings Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate? Conclusions and Significance We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites.
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              Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells.

              Although TNF is a major proinflammatory cytokine, increasing evidence indicates that TNF also has immunosuppressive feedback effects. We have demonstrated in this study that, in both resting and activated states, mouse peripheral CD4(+)CD25(+) T regulatory cells (Tregs) expressed remarkably higher surface levels of TNFR2 than CD4(+)CD25(-) T effector cells (Teffs). In cocultures of Tregs and Teffs, inhibition of proliferation of Teffs by Tregs was initially transiently abrogated by exposure to TNF, but longer exposure to TNF restored suppressive effects. Cytokine production by Teffs remained continually suppressed by Tregs. The profound anergy of Tregs in response to TCR stimulation was overcome by TNF, which expanded the Treg population. Furthermore, in synergy with IL-2, TNF expanded Tregs even more markedly up-regulated expression of CD25 and FoxP3 and phosphorylation of STAT5, and enhanced the suppressive activity of Tregs. Unlike TNF, IL-1beta and IL-6 did not up-regulate FoxP3-expressing Tregs. Furthermore, the number of Tregs increased in wild-type mice, but not in TNFR2(-/-) mice following sublethal cecal ligation and puncture. Depletion of Tregs significantly decreased mortality following cecal ligation and puncture. Thus, the stimulatory effect of TNF on Tregs resembles the reported costimulatory effects of TNF on Teffs, but is even more pronounced because of the higher expression of TNFR2 by Tregs. Moreover, our study suggests that the slower response of Tregs than Teffs to TNF results in delayed immunosuppressive feedback effects.

                Author and article information

                Journal
                Iran J Parasitol
                Iran J Parasitol
                IJPA
                IJPA
                Iranian Journal of Parasitology
                Tehran University of Medical Sciences
                1735-7020
                2008-238X
                Jul-Sep 2021
                : 16
                : 3
                : 490-498
                Affiliations
                [1. ] Department of Microbiology, School of Basic Sciences, Hamedan Branch, Islamic Azad University, Hamedan, Iran
                [2. ] Department of Biology, Faculty of Education, Herat University, Herat, Afghanistan
                [3. ] Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
                [4. ] Medical Laboratory Department, Laboratory Expert, University of Medical Sciences, Hamedan, Iran
                [5. ] Department of Laboratory Sciences, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran
                [6. ] Department of Microbiology, Fasa University of Medical Sciences, Fasa, Iran
                [7. ] Nursing Department, Basic Sciences Faculty, Hamedan Branch, Islamic Azad University, Hamedan, Iran
                Author notes
                [* ] Correspondence Email: Hossein_vazini@ 123456yahoo.com
                Article
                IJPA-16-490
                10.18502/ijpa.v16i3.7103
                8476719
                34630595
                7bcec13b-4d93-406f-a7b3-5fe8a3dedec2
                Copyright © 2021 Taraghian et al. Published by Tehran University of Medical Sciences

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 22 January 2021
                : 10 April 2021
                Categories
                Original Article

                Parasitology
                cutaneous leishmaniasis,ifn-gamma,tnf-alpha,iinterlokin-10,immunological response
                Parasitology
                cutaneous leishmaniasis, ifn-gamma, tnf-alpha, iinterlokin-10, immunological response

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