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      Is There Any Difference between the In Situ and Systemic IL-10 and IFN-γ Production when Clinical Forms of Cutaneous Sporotrichosis Are Compared?

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          Abstract

          Fungus of the Sporothrix schenckii complex can produce skin lesions in humans, commonly lymphocutaneous (LC) and fixed (F) forms of sporotrichosis. Some authors have suggested that clinical forms are influenced by differences in virulence and genetic profile of isolates. But little is known about the role of immune response in determining the clinical outcome of sporotrichosis. To verify the profile of systemic and in situ IFN-γ and IL-10 expression in sporotrichosis patients, and consequently to detect any difference between the two compartments and/or clinical presentation, we quantified the number of IFN-γ and IL-10 producer peripheral blood mononuclear cells stimulated with S. schenckii antigen (Ss-Ag) by Elispot, and quantified cytokines expression by in situ immunohistochemistry in the same patient. Three groups were formed: 1- LC (n = 9); 2- F (n = 10); 3- healthy individuals (n = 14). All sporotrichosis patients produced high amounts of systemic IFN- γ when compared to uninfected individuals. No differences were observed between LC and F groups. Regarding in situ IL-10 expression, a difference between LC and F groups was observed: LC lesions presented higher amounts of IL-10 than F lesions differently from systemic IL-10 which showed similarities. Our data suggests that LC lesions present higher IL-10 expression which could be related to regulatory mechanisms for compensating the tissue injury, however favoring fungal persistence in the lesions. Surprisingly, there were no differences in systemic and in situ IFN- γ expression between CL and F patients, although it was significantly higher expressed in these patients than in healthy individuals.

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          Most cited references 38

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          Immune recognition of Candida albicans beta-glucan by dectin-1.

          Beta (1,3)-glucans represent 40% of the cell wall of the yeast Candida albicans. The dectin-1 lectin-like receptor has shown to recognize fungal beta (1,3)-glucans and induce innate immune responses. The importance of beta-glucan-dectin-1 pathways for the recognition of C. albicans by human primary blood cells has not been firmly established. In this study we demonstrate that cytokine production by both human peripheral blood mononuclear cells and murine macrophages is dependent on the recognition of beta-glucans by dectin-1. Heat killing of C. albicans resulted in exposure of beta-glucans on the surface of the cell wall and subsequent recognition by dectin-1, whereas live yeasts stimulated monocytes mainly via recognition of cell-surface mannans. Dectin-1 induced cytokine production through the following 2 pathways: Syk-dependent production of the T-helper (Th) 2-type anti-inflammatory cytokine interleukin-10 and Toll-like receptor-Myd88-dependent stimulation of monocyte-derived proinflammatory cytokines, such as tumor necrosis factor-alpha . In contrast, stimulation of Th1-type cytokines, such as interferon-gamma , by C. albicans was independent of the recognition of beta-glucans by dectin-1. In conclusion, C. albicans induces production of monocyte-derived and T cell-derived cytokines through distinct pathways dependent on or independent of dectin-1.
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            Cat-transmitted sporotrichosis epidemic in Rio de Janeiro, Brazil: description of a series of cases.

            Sporotrichosis is the most common subcutaneous mycosis in South America. Classic infection is associated with traumatic inoculation of soil, vegetables, and organic matter contaminated with Sporothrix schenckii. Zoonotic transmission has been described in isolated cases or in small outbreaks. Since 1998, we have been observing an increasing number of cases of sporotrichosis in persons from the city of Rio de Janeiro, Brazil, and surroundings. From 1998 to 2001, 178 cases of culture-proven sporotrichosis had been diagnosed. Female patients predominated, and the median age was 39 years. The most frequent clinical presentation was lymphocutaneous disease. Of the 178 patients, 156 reported domiciliary or professional contact with cats with sporotrichosis, and 97 of these patients had a history of receipt of cat scratch or bite. The patients received itraconazole as first-line treatment. This study suggests that feline transmission of sporotrichosis was associated with a large and long-lasting outbreak of the disease in Rio de Janeiro.
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              Emergence of pathogenicity in the Sporothrix schenckii complex.

              Sporothrix schenckii sensu lato is a complex of thermally dimorphic species whose natural habitats are soil and plant materials. However, the traumatic implantation of the species into human skin is traditionally thought to be the route leading to the fungal disease sporotrichosis. The complex contains Sporotrhix mexicana, S. globosa, S. brasiliensis, S. luriei, in addition to S. schenckii sensu stricto. In this study we evaluated the differences among these species relative to their frequency in the environment and in human hosts, as well as discuss their remarkable diverse pathogenicity. Today, S. brasiliensis is epidemic in and geographically restricted to Brazil. In contrast, S. mexicana and S. globosa have rarely been reported over the decades. We discovered that the species have been present in collections from clinical cases since 1955 and were able to re-identify six isolates originally classified as S. schenckii as Sporothrix mexicana (three isolates) and Sporothrix globosa (three isolates). Despite their long presence as potential human pathogens they have not shown any increase in frequency as etiologic agents of human infections.
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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, CA USA )
                1932-6203
                13 September 2016
                2016
                : 11
                : 9
                Affiliations
                [1 ]Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, RJ, Brazil
                [2 ]VigiLeish-Serviço de Infectologia, Instituto Nacional de Infectologia Evandro Chagas/FIOCRUZ, Rio de Janeiro, RJ, Brazil
                [3 ]Departamento de Otorrinolaringologia-Oftalmologia/Faculdade de Medicina/Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
                Mie University Graduate School of Medicine, JAPAN
                Author notes

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

                • Conceived and designed the experiments: FCS FNM.

                • Performed the experiments: FNM AOS MIP MRL ECFV CMVR FCS.

                • Analyzed the data: FNM FCS.

                • Contributed reagents/materials/analysis tools: FNM AOS FCS.

                • Wrote the paper: FNM AOS MIP MRL ECFV CMVR FCS.

                [¤a]

                Current address: Laboratório de Pesquisa em Leishmaniose, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, RJ, Brazil

                [¤b]

                Current address: Hygiene and Tropical Medicine Institute (IHMT), New University of Lisbon (UNL), Lisbon, Portugal

                Article
                PONE-D-16-11488
                10.1371/journal.pone.0162764
                5021344
                27622513
                © 2016 Morgado et al

                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.

                Page count
                Figures: 2, Tables: 3, Pages: 11
                Product
                Funding
                Funded by: IOC-FIOCRUZ
                Award Recipient : Fatima Conceição-Silva
                Funded by: INI-FIOCRUZ
                Award Recipient :
                Funded by: PROEP-IOC-CNPq
                Award ID: 402557/2011-5
                Award Recipient : Fatima Conceição-Silva
                Funded by: PAEF-IOC-Fiotec
                Award ID: IOC-008-FIO-15
                Award Recipient : Fatima Conceição-Silva
                Funded by: FAPERJ
                Award ID: E26/111.230/2014
                Award Recipient : Fatima Conceição-Silva
                This work was supported by Instituto Oswaldo Cruz-Fundação Oswaldo Cruz, obtained by FCS; Instituto Nacional de Infectologia Evandro Chagas-Fundação Oswaldo Cruz, obtained by AOS; Programa de Excelência em Pesquisa-Instituto Oswaldo Cruz-Fundação Oswaldo Cruz-Conselho Nacional de Desenvolvimento Científico e Tecnológico (402557/2011-5), obtained by FCS; Ações Estratégicas para o Desenvolvimento e Fortalecimento dos Laboratórios Credenciados e das Áreas de Apoio à Pesquisa do Instituto Oswaldo Cruz-Fundação para o desenvolvimento Científico e Tecnológico em Saúde (IOC-008-FIO-15), obtained by FCS; and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (E26/111.230/2014), obtained by FCS. AOS is a recipient of fellowships from CNPq and FAPERJ. CMVR is a recipient of FAPERJ fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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