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      Potential Role of CXCL10 in Monitoring Response to Treatment in Leprosy Patients

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          Abstract

          The treatment of multibacillary cases of leprosy with multidrug therapy (MDT) comprises 12 doses of a combination of rifampicin, dapsone and clofazimine. Previous studies have described the immunological phenotypic pattern in skin lesions in multibacillary patients. Here, we evaluated the effect of MDT on skin cell phenotype and on the Mycobacterium leprae-specific immune response. An analysis of skin cell phenotype demonstrated a significant decrease in MRS1 (SR-A), CXCL10 (IP-10) and IFNG (IFN-γ) gene and protein expression after MDT release. Patients were randomized according to whether they experienced a reduction in bacillary load after MDT. A reduction in CXCL10 (IP-10) in sera was associated with the absence of a reduction in the bacillary load at release. Although IFN-γ production in response to M. leprae was not affected by MDT, CXCL10 (IP-10) levels in response to M. leprae increased in cells from patients who experienced a reduction in bacillary load after treatment. Together, our results suggest that CXCL10 (IP-10) may be a good marker for monitoring treatment efficacy in multibacillary patients.

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          Exploring the full spectrum of macrophage activation.

          Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.
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            Cutaneous wound healing.

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              Macrophage phenotypes during tissue repair.

              Mp are crucial for tissue repair and regeneration but can also contribute to tissue damage and fibrosis. Mp can adopt a variety of functional phenotypes in response to different stimuli; two of the best-characterized in vitro phenotypes are a proinflammatory "M1" phenotype, produced by exposure to IFN-γ and TNF-α, and an anti-inflammatory "M2a" phenotype, produced by IL-4 or IL-13. M2a Mp are frequently termed "wound healing" Mp, as they express factors that are important for tissue repair. This review will summarize current knowledge of Mp phenotypes during tissue repair and will argue that these in vivo Mp populations are heterogeneous and temporally regulated and do not conform to existing, in vitro-defined M1 or M2 phenotypes. Mp during the early stages of tissue repair exhibit a more proinflammatory phenotype than their later counterparts, which in turn may exhibit some M2a-associated characteristics. However, phenotypic markers that appear to be coregulated in cultured Mp can be expressed independently of each other in vivo. Additionally, M1- and M2-associated markers may be expressed simultaneously by actual tissue-repair Mp. Improved understanding of Mp phenotypes and their regulation may assist in generation of novel therapies based on manipulating Mp function to improve healing.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1237431
                URI : https://loop.frontiersin.org/people/480246
                URI : https://loop.frontiersin.org/people/404337
                URI : https://loop.frontiersin.org/people/415453
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                20 July 2021
                2021
                : 12
                : 662307
                Affiliations
                [1] 1 Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation , Rio de Janeiro, Brazil
                [2] 2 Cascalho-Platt Laboratory, Department of Surgery, University of Michigan , Ann Arbor, MI, United States
                Author notes

                Edited by: Nathalie Winter, Institut National de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), France

                Reviewed by: Utpal Sengupta, The Leprosy Mission Trust India, India; Patrick Brennan, Colorado State University, United States

                *Correspondence: Roberta Olmo Pinheiro, robertaolmo@ 123456gmail.com

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.662307
                8329534
                34354699
                3c2ec13e-e6f9-43dd-8737-0fbfe74c3075
                Copyright © 2021 Ferreira, Mendes, de Mattos Barbosa, de Oliveira, Sales, Moraes, Sarno and Pinheiro

                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
                : 01 February 2021
                : 05 July 2021
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 64, Pages: 10, Words: 4381
                Categories
                Immunology
                Original Research

                Immunology
                leprosy,skin cells,ifn-γ,cxcl-10,multidrug therapy
                Immunology
                leprosy, skin cells, ifn-γ, cxcl-10, multidrug therapy

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