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      Expression of Pro-inflammatory Genes in Lesions and Neutrophils during Leishmania major Infection in BALB/c Mice

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          Abstract

          Background:

          Leishmaniasis is a worldwide disease prevalent in tropical and sub-tropical countries in the world. Characterization of inflammatory responses produced in cutaneous leishmaniasis has not yet been completed.

          Methods:

          The specific primers were designed for ten pro-inflammatory genes including CCL4, CCL3, TNF-α, IL-1α, IL-12P35, IL-12P40, CCL5, CCR5, IL-1β and IFN- γ and their expression were assessed and compared using RT-PCR in the lesion and peripheral blood neutrophils in Leishmania infected BALB/c mice.

          Results:

          None of the pro-inflammatory genes was expressed in the healthy tissue and except IFN-γ others were down-regulated by the parasite in the lesion in untreated mice. In mice treated with anti-Leishmanial drugs, the expression of the pro-inflammatory genes restarted. The figure of pro-inflammatory gene expression in neutrophils was different was from the lesions in treated and untreated mice.

          Conclusion:

          Leishmania is capable to suppress the expression of pro-inflammatory genes in the lesions but not in neutrophils. The expression of TNF-α in the lesions and down-regulation of IL-1β in neutrophils could be accounted as an indication for healing of cutaneous leishmaniasis. The results open a new window on characterization of Leishmania lesions and clarifying the role of neutrophils in Leishmania infections.

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          Most cited references12

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          The role of chemokines in linking innate and adaptive immunity.

          It is becoming clear that chemokine function is necessary to translate an innate-immune response into an acquired response. Dendritic cells activated by innate stimuli and loaded with foreign antigen travel to regional lymph nodes to activate the acquired-immune system. Subsequently, the activated acquired-immune cells move into tissue, where the innate immune system sets-off the danger signal. The chemokine system has emerged as an essential regulator of this dendritic cell and lymphocyte trafficking, which is necessary to turn an innate immune response into an adaptive response.
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            Neutrophils and macrophages cooperate in host resistance against Leishmania braziliensis infection.

            Neutrophils play an active role in the control of infections caused by intracellular pathogens such as Leishmania. In the present study, we investigated the effect of neutrophil depletion at the time of Leishmania braziliensis infection of BALB/c mice and how neutrophils interact with the infected macrophage to promote parasite elimination. The in vivo depletion of neutrophils led to a significant increase in parasite load and enhanced the Th1-Th2 immune response in this experimental model of infection. BALB/c mice coinoculated with both parasites and live neutrophils displayed lower parasite burdens at the site of infection and in the draining lymph nodes. In vitro, we observed that live neutrophils significantly reduced the parasite load in L. braziliensis-infected murine macrophages, an effect not observed with Leishmania major. L. braziliensis elimination was dependent on the interaction between neutrophils and macrophages and was associated with TNF-alpha as well as superoxide production. Furthermore, cooperation between neutrophils and macrophages toward parasite elimination was also observed in experiments performed with L. braziliensis-infected human cells and, importantly, with two other New World Leishmania species. These results indicate that neutrophils play an important and previously unappreciated role in L. braziliensis infection, favoring the induction of a protective immune response.
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              Permissive and protective roles for neutrophils in leishmaniasis.

              Leishmania parasites are the causative agents of leishmaniasis, a neglected tropical disease that causes substantial morbidity and considerable mortality in many developing areas of the world. Recent estimates suggest that roughly 10 million people suffer from cutaneous leishmaniasis (CL), and approximately 76,000 are afflicted with visceral leishmaniasis (VL), which is universally fatal without treatment. Efforts to develop therapeutics and vaccines have been greatly hampered by an incomplete understanding of the parasite's biology and a lack of clear protective correlates that must be met in order to achieve immunity. Although parasites grow and divide preferentially in macrophages, a number of other cell types interact with and internalize Leishmania parasites, including monocytes, dendritic cells and neutrophils. Neutrophils appear to be especially important shortly after parasites are introduced into the skin, and may serve a dual protective and permissive role during the establishment of infection. Curiously, neutrophil recruitment to the site of infection appears to continue into the chronic phase of disease, which may persist for many years. The immunological impact of these cells during chronic leishmaniasis is unclear at this time. In this review we discuss the ways in which neutrophils have been observed to prevent and promote the establishment of infection, examine the role of anti-neutrophil antibodies in mouse models of leishmaniasis and consider recent findings that neutrophils may play a previously unrecognized role in influencing chronic parasite persistence.
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                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
                Oct-Dec 2016
                : 11
                : 4
                : 534-541
                Affiliations
                [1. ] Dept. of Laboratory Sciences, School of Veterinary Sciences, Bu-Ali Sina University, Hamadan, Iran
                [2. ] Dept. of Clinical Sciences, Faculty of Para-Veterinary Sciences, Bu-Ali Sina University, Hamedan, Iran
                Author notes
                [* ] Correspondence Email: hrezvan@ 123456gmail.com
                Article
                ijpa-11-534
                5251182
                d5c6689d-c82b-4983-86c3-d2ed77565dfe
                Copyright© Iranian Society of Parasitology & Tehran University of Medical Sciences

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

                History
                : 06 November 2015
                : 17 April 2016
                Categories
                Original Article

                Parasitology
                leishmania,pro-inflammatory genes,neutrophils,lesion,balb/c mice
                Parasitology
                leishmania, pro-inflammatory genes, neutrophils, lesion, balb/c mice

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