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      Clinical and immunological spectra of human cutaneous leishmaniasis in North Africa and French Guiana

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          Abstract

          Cutaneous leishmaniasis (CL) caused by infection with the parasite Leishmania exhibits a large spectrum of clinical manifestations ranging from single healing to severe chronic lesions with the manifestation of resistance or not to treatment. Depending on the specie and multiple environmental parameters, the evolution of lesions is determined by a complex interaction between parasite factors and the early immune responses triggered, including innate and adaptive mechanisms. Moreover, lesion resolution requires parasite control as well as modulation of the pathologic local inflammation responses and the initiation of wound healing responses. Here, we have summarized recent advances in understanding the in situ immune response to cutaneous leishmaniasis: i) in North Africa caused by Leishmania (L.) major, L. tropica, and L. infantum, which caused in most cases localized autoresolutives forms, and ii) in French Guiana resulting from L. guyanensis and L. braziliensis, two of the most prevalent strains that may induce potentially mucosal forms of the disease. This review will allow a better understanding of local immune parameters, including cellular and cytokines release in the lesion, that controls infection and/or protect against the pathogenesis in new world compared to old world CL.

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          Leishmaniasis

          Leishmaniasis is a poverty-related disease with two main clinical forms: visceral leishmaniasis and cutaneous leishmaniasis. An estimated 0·7-1 million new cases of leishmaniasis per year are reported from nearly 100 endemic countries. The number of reported visceral leishmaniasis cases has decreased substantially in the past decade as a result of better access to diagnosis and treatment and more intense vector control within an elimination initiative in Asia, although natural cycles in transmission intensity might play a role. In east Africa however, the case numbers of this fatal disease continue to be sustained. Increased conflict in endemic areas of cutaneous leishmaniasis and forced displacement has resulted in a surge in these endemic areas as well as clinics across the world. WHO lists leishmaniasis as one of the neglected tropical diseases for which the development of new treatments is a priority. Major evidence gaps remain, and new tools are needed before leishmaniasis can be definitively controlled.
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            CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity.

            The long-term persistence of pathogens in a host that is also able to maintain strong resistance to reinfection, referred to as concomitant immunity, is a hallmark of certain infectious diseases, including tuberculosis and leishmaniasis. The ability of pathogens to establish latency in immune individuals often has severe consequences for disease reactivation. Here we show that the persistence of Leishmania major in the skin after healing in resistant C57BL/6 mice is controlled by an endogenous population of CD4+CD25+ regulatory T cells. These cells constitute 5-10% of peripheral CD4+ T cells in naive mice and humans, and suppress several potentially pathogenic responses in vivo, particularly T-cell responses directed against self-antigens. During infection by L. major, CD4+CD25+ T cells accumulate in the dermis, where they suppress-by both interleukin-10-dependent and interleukin-10-independent mechanisms-the ability of CD4+CD25- effector T cells to eliminate the parasite from the site. The sterilizing immunity achieved in mice with impaired IL-10 activity is followed by the loss of immunity to reinfection, indicating that the equilibrium established between effector and regulatory T cells in sites of chronic infection might reflect both parasite and host survival strategies.
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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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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                27 July 2023
                2023
                : 14
                : 1134020
                Affiliations
                [1] 1 Univ. Lille, Univ. French Guiana, CNRS UMR 9017-INSERM U1019, Center for Infection and Immunity of Lille-CIIL, Institut Pasteur de Lille , Lille, France
                [2] 2 Laboratoire de Recherche, LR 16-IPT-06, Parasitoses Médicales, Biotechnologies et Biomolécules, Institut Pasteur de Tunis, Université Tunis El-Manar , Tunis, Tunisia
                [3] 3 Centre National de Référence des Leishmanioses, Laboratoire Associé, Hôpital Andrée Rosemon , Cayenne, French Guiana, France
                [4] 4 Service de Dermatologie, Hôpital de Cayenne , Cayenne, French Guiana, France
                [5] 5 Service de Parasitologie-Mycologie, Institut Pasteur de Tunis , Tunis, Tunisia
                Author notes

                Edited by: Denis Sereno, Institut de Recherche Pour le Développement (IRD), France

                Reviewed by: Fernanda Nazaré Morgado, Oswaldo Cruz Institute, Brazil; Sara M. Robledo, University of Antioquia, Colombia

                *Correspondence: Sylviane Pied, sylviane.pied@ 123456pasteur-lille.fr
                Article
                10.3389/fimmu.2023.1134020
                10421664
                37575260
                3f9faf4f-0cd8-4bc7-9898-56d53e4636b9
                Copyright © 2023 Saidi, Blaizot, Prévot, Aoun, Demar, Cazenave, Bouratbine and Pied

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 December 2022
                : 10 March 2023
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 150, Pages: 13, Words: 5149
                Funding
                This work was supported by LabEx PARAFRAP ANR-11-LABX-0024i and MALTOX FEDER CTG Guyane.
                Categories
                Immunology
                Review
                Custom metadata
                Parasite Immunology

                Immunology
                l. major,l. infantum,l. tropica,l. guyanensis,l. braziliensis,cutaneous leishmaniasis (cl),clinical manifestation,local immune response

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