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      Sporothrix schenckii Immunization, but Not Infection, Induces Protective Th17 Responses Mediated by Circulating Memory CD4 + T Cells

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          Abstract

          Sporotrichosis is a chronic subcutaneous mycosis caused by the Sporothrix schenckii species complex and it is considered an emerging opportunistic infection in countries with tropical and subtropical climates. The host’s immune response has a main role in the development of this disease. However, it is unknown the features of the memory cellular immune response that could protect against the infection. Our results show that i.d. immunization in the ears of mice with inactivated S. schenckii conidia (iC) combined with the cholera toxin (CT) induces a cellular immune response mediated by circulating memory CD4 + T cells, which mainly produce interleukin 17 (IL-17). These cells mediate a strong delayed-type hypersensitivity (DTH) reaction. Systemic and local protection against S. schenckii was mediated by circulating CD4 + T cells. In contrast, the infection induces a potent immune response in the skin mediated by CD4 + T cells, which have an effector phenotype that preferentially produce interferon gamma (IFN-γ) and mediate a transitory DTH reaction. Our findings prove the potential value of the CT as a potent skin adjuvant when combined with fungal antigens, and they also have important implications for our better understanding of the differences between the memory immune response induced by the skin immunization and those induced by the infection; this knowledge enhances our understanding of how a protective immune response against a S. schenckii infection is developed.

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          Most cited references 48

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          Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection.

          We identify in this article a new class of lung tissue-resident memory CD4 T cells that exhibit tissue tropism and retention independent of Ag or inflammation. Tissue-resident memory CD4 T cells in the lung did not circulate or emigrate from the lung in parabiosis experiments, were protected from in vivo Ab labeling, and expressed elevated levels of CD69 and CD11a compared with those of circulating memory populations. Importantly, influenza-specific lung-resident memory CD4 T cells served as in situ protectors to respiratory viral challenge, mediating enhanced viral clearance and survival to lethal influenza infection. By contrast, memory CD4 T cells isolated from spleen recirculated among multiple tissues without retention and failed to mediate protection to influenza infection, despite their ability to expand and migrate to the lung. Our results reveal tissue compartmentalization as a major determining factor for immune-mediated protection in a key mucosal site, important for targeting local protective responses in vaccines and immunotherapies.
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            Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection.

            Heterogeneity is a hallmark of the adaptive immune system. This is most evident in the enormous diversity of B and T cell antigen receptors. There is also heterogeneity within antiviral T cell populations, and subsets of effector and memory T cells now permeate our thinking about specialization of T cell responses to pathogens. It has been less clear, however, how heterogeneity in developing virus-specific effector and memory T cells is related to cell-fate decisions in the immune response, such as the generation long-lived memory T cells. Here we discuss recent findings that might help redefine how heterogeneity in antiviral T cell populations gives rise to T cell subsets with short- and long-lived cell fates.
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              Sporothrix brasiliensis, S. globosa, and S. mexicana, three new Sporothrix species of clinical interest.

              Sporothrix schenckii is the species responsible for sporotrichosis, a fungal infection caused by the traumatic implantation of this dimorphic fungus. Recent molecular studies have demonstrated that this species constitutes a complex of numerous phylogenetic species. Since the delineation of such species could be of extreme importance from a clinical point of view, we have studied a total of 127 isolates, most of which were received as S. schenckii, including the available type strains of species currently considered synonyms, and also some close morphological species. We have phenotypically characterized all these isolates using different culture media, growth rates at different temperatures, and numerous nutritional tests and compared their calmodulin gene sequences. The molecular analysis revealed that Sporothrix albicans, S. inflata, and S. schenckii var. luriei are species that are clearly different from S. schenckii. The combination of these phenetic and genetic approaches allowed us to propose the new species Sporothrix brasiliensis, S. globosa, and S. mexicana. The key phenotypic features for recognizing these species are the morphology of the sessile pigmented conidia, growth at 30, 35, and 37 degrees C, and the assimilation of sucrose, raffinose, and ribitol.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                12 June 2018
                2018
                : 9
                Affiliations
                1Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City, Mexico
                2Facultad de Medicina, Universidad Nacional Autónoma de México , Mexico City, Mexico
                3Laboratorio de Micología Básica, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México , Mexico City, Mexico
                Author notes

                Edited by: Hector Mora Montes, Universidad de Guanajuato, Mexico

                Reviewed by: Luis Antonio Pérez-García, Universidad Autónoma de San Luis Potosí, Mexico; José Ascención Martínez-Álvarez, Universidad de Guanajuato, Mexico; Delia Vanessa Lopez Guerrero, Universidad Autónoma del Estado de Morelos, Mexico

                *Correspondence: Laura C. Bonifaz, labonifaz@ 123456yahoo.com

                This article was submitted to Fungi and Their Interactions, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2018.01275
                6005866
                Copyright © 2018 García-Lozano, Toriello, Antonio-Herrera and Bonifaz.

                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 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.

                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 51, Pages: 14, Words: 0
                Categories
                Microbiology
                Original Research

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