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      Monocyte-Derived Dendritic Cells from Patients with Dermatophytosis Restrict the Growth of Trichophyton rubrum and Induce CD4-T Cell Activation

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          Abstract

          Dermatophytes are the most common agents of superficial mycoses that are caused by mold fungi. Trichophyton rubrum is the most common pathogen causing dermatophytosis. The immunology of dermatophytosis is currently poorly understood. Recently, our group investigated the interaction of T. rubrum conidia with peritoneal mouse macrophages. We found that macrophages phagocytose T. rubrum conidia resulted in a down-modulation of class II major histocompatibility complex (MHC) antigens and in the expression of co-stimulatory molecules. Furthermore, it induced the production of IL-10, and T. rubrum conidia differentiated into hyphae that grew and killed the macrophages after 8 hrs of culture. This work demonstrated that dendritic cells (DCs) and macrophages, from patients or normal individuals, avidly interact with pathogenic fungus T. rubrum. The dermatophyte has two major receptors on human monocyte-derived DC: DC-SIGN and mannose receptor. In contrast macrophage has only mannose receptor that participates in the phagocytosis or bound process. Another striking aspect of this study is that unlike macrophages that permit rapid growth of T. rubrum, human DC inhibited the growth and induces Th activation. The ability of DC from patients to interact and kill T. rubrum and to present Ags to T cells suggests that DC may play an important role in the host response to T. rubrum infection by coordinating the development of cellular immune response.

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          Most cited references20

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          Immunity to fungal infections.

          The topic of immunity to fungal infections is of interest to a wide range of disciplines, from microbiology to immunology. It is of particular interest in terms of therapy of HIV-infected individuals, and patients with cancer or individuals who have received transplants. Understanding the nature and function of the immune response to fungi is an exciting challenge that might set the stage for new approaches to the treatment of fungal diseases, from immunotherapy to vaccines. The past decade has witnessed the development of a wide range of new approaches to elucidate events that occur at the host-fungus interface.
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            The C-type lectin DC-SIGN (CD209) is an antigen-uptake receptor for Candida albicans on dendritic cells.

            Dendritic cells (DC) that express the type II C-type lectin DC-SIGN (CD209) are located in the submucosa of tissues, where they mediate HIV-1 entry. Interestingly, the pathogen Candida albicans, the major cause of hospital-acquired fungal infections, penetrates at similar submucosal sites. Here we demonstrate that DC-SIGN is able to bind C. albicans both in DC-SIGN-transfected cell lines and in human monocyte-derived DC. The binding was shown to be time- as well as concentration-dependent, and live as well as heat-inactivated C. albicans were bound to the same extent. Moreover, in immature DC, DC-SIGN was able to internalize C. albicans in specific DC-SIGN-enriched vesicles, distinct from those containing the mannose receptor, the other known C. albicans receptor expressed by DC. Together, these results demonstrate that DC-SIGN is an exquisite pathogen-uptake receptor that captures not only viruses but also fungi.
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              Signalling C-Type lectin receptors, microbial recognition and immunity

              Signalling C-type lectin receptors (CLRs) are crucial in shaping the immune response to fungal pathogens, but comparably little is known about the role of these receptors in bacterial, viral and parasitic infections. CLRs have many diverse functions depending on the signalling motifs in their cytoplasmic domains, and can induce endocytic, phagocytic, antimicrobial, pro-inflammatory or anti-inflammatory responses which are either protective or not during an infection. Understanding the role of CLRs in shaping anti-microbial immunity offers great potential for the future development of therapeutics for disease intervention. In this review we will focus on the recognition of bacterial, viral and parasitic pathogens by CLRs, and how these receptors influence the outcome of infection. We will also provide a brief update on the role of CLRs in antifungal immunity.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                5 November 2014
                : 9
                : 11
                : e110879
                Affiliations
                [1 ]Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil
                [2 ]Departamento de Dermatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
                Institut de Pharmacologie et de Biologie Structurale, France
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SRA PC. Performed the experiments: KS GFB. Analyzed the data: KS GFB PC SRA. Contributed reagents/materials/analysis tools: SRA. Contributed to the writing of the manuscript: SRA.

                [¤]

                Current address: Universidade Federal de Mato Grosso, Rondonópolis, Mato Grosso, Brazil

                Article
                PONE-D-14-26528
                10.1371/journal.pone.0110879
                4220947
                25372145
                c1ebcef7-7138-45f7-8121-388168fb372f
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 June 2014
                : 20 September 2014
                Page count
                Pages: 8
                Funding
                The work was supported by grants from the following: Fundação de Aparo a Pesquisa do Estado de São Paulo (FAPESP) and Concelho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Immunology
                Medicine and Health Sciences
                Infectious Diseases
                Fungal Diseases
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.

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