Host organism defense by a peptide-polysaccharide extracted from the fungus Sporothrix schenckii

A peptide-polysaccharide, a peptide-rhamnomannan, was isolated from the pathogenic yeast form of the fungus Sporothrix schenckii. This substance, which may play a role in fungal virulence, was tested in an animal model of systemic disease, and depression of the immune response was observed in the animals between the 4th and 6th week of infection. Concomitantly, this compound showed mitogenic activity when challenged with normal lymphocytes and was also found to be involved in the inflammatory response. These results provide further information for the understanding of fungal implantation in tissues and of the pathogenicity of this systemic mycosis.

Isolation of ergosterol peroxide and its reversion to ergosterol in the pathogenic fungus Sporothrix schenckii

Ergosterol peroxide, a presumed product of the H2O2-dependent enzymatic oxidation of ergosterol, has been isolated from yeast from yeast forms of the pathogenic fungus Sporothrix schenckii. The substance, which may have a role in fungal virulence, has been characterized mainly using spectroscopic methods (1H and 13C nuclear magnetic resonance and high resolution mass spectra). The purified compound showed a molecular formula of C28H44O3, displaying characteristic features of epidioxy sterols and was reverted to ergosterol when submitted to S. schenckii enzymatic extract.

Role of TLR-2 and fungal surface antigens on innate immune response against Sporothrix schenckii

Sporotrichosis is an infection caused by the dimorphic fungus Sporothrix schenckii. Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 and fungal surface antigens in the recognition of S. schenckii and in the subsequent immune response. This study aimed to evaluate the involvement of TLR-2 and fungal surface soluble (SolAg) and lipidic (LipAg) antigens in phagocytosis of S. schenckii and production of immune mediators by macrophages obtained from WT and TLR-2 -/- animals. The results showed that TLR-2-/- animals had had statistical lower percentage of macrophages with internalized yeasts compared to WT. SolAg and LipAg impaired phagocytosis and immunological mediator production for both WT and TLR-2-/-. The absence of TLR-2 led to lower production of the cytokines TNF, IL-1β, IL-12 and IL-10 compared to WT animals. These results suggest a new insight in relation to how the immune system, through TLR-2, recognizes and induces the production of mediators in response to the fungus S. schenckii. Copyright © Informa Healthcare USA, Inc.

The Predominance of Alternatively Activated Macrophages Following Challenge with Cell Wall Peptide-Polysaccharide After Prior Infection with Sporothrix schenckii

Sporotrichosis is a subcutaneous mycosis that is caused by the dimorphic fungus Sporothrix schenckii. This disease generally occurs within the skin and subcutaneous tissues, causing lesions that can spread through adjacent lymphatic vessels and sometimes leading to systemic diseases in immunocompromised patients. Macrophages are crucial for proper immune responses against a variety of pathogens. Furthermore, macrophages can play different roles in response to different microorganisms and forms of activation, and they can be divided into classic or alternatively activated populations, as also known as M1 and M2 macrophages. M1 cells can lead to tissue injury and contribute to pathogenesis, whereas M2 cells promote angiogenesis, tissue remodeling, and repair. The aim of this study was to investigate the roles of M1 and M2 macrophages in a sporotrichosis model. Toward this end, we performed phenotyping of peritoneal exudate cells and evaluated the concomitant production of several immunomediators, including IL-12, IL-10, TGF-β, nitric oxide, and arginase-I activity, which were stimulated ex vivo with cell wall peptide-polysaccharide. Our results showed the predominance of the M2 macrophage population, indicated by peaks of arginase-I activity as well as IL-10 and TGF-β production during the 6th and 8th weeks after infection. These results were consistent with cellular phenotyping that revealed increases in CD206-positive cells over this period. This is the first report of the participation of M2 macrophages in sporotrichosis infections. © 2013 Springer Science+Business Media Dordrecht.

Envolvimento do inflamassoma e citocinas na resposta imunológica em infecção induzida pelo fungo Sporothrix schenckii

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Influência do receptor Toll-like 2 na defesa do hospedeiro contra o fungo Sporothrix schenckii

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise dos macrófagos M1 e M2 durante a infecção por Sporothrix schenckii em modelo murino

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sporothrix schenckii sensu stricto Isolated from Soil in an Armadillo's Burrow

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência do receptor TLR-2 no processo de fagocitose do fungo Sporothrix schenckii

A esporotricose é uma micose provocada pelo fungo Sporothrix schenckii, resultante da inoculação direta de conídios e hifas do fungo. A doença se desenvolve habitualmente na pele, no tecido subcutâneo, podendo através dos vasos linfáticos, comprometer órgãos internos. Nos últimos anos tem-se voltado à atenção à participação do receptor Toll Like-2 no reconhecimento e fagocitose de diversos antígenos fungicos. A partir disto, o objetivo deste estudo foi estudar a influência do receptor Toll Like-2 no processo de fagocitose do Sporothrix schenckii em camundongos C57BL/6. Este estudo avaliou o processo de internalização do Sporothrix schenckii por macrófagos murinos obtidos de camundongos C57BL/6 WT e C57BL/6 TLR-2 KO. Os experimentos foram realizados através da utilização de lâminas de cultura celular e microscopia ótica. Além de analisar a viabilidade de células fúngicas internalizadas através de ensaios de sobrevivência. Como resultados pudemos observar a significativa importância do TLR-2 no processo de internalização deste microrganismo, uma vez que o estudo evidenciou uma eficácia de internalização acima de 85% dos macrófagos obtidos de animas selvagens em relação aos obtidos de animais TLR-2 KO. Além disso, através de ensaios de sobrevivência foram obtidos resultados que sugerem a ausência de viabilidade das células fúngicas depois de fagocitadas

Involvement of major components from sporothrix schenckii cell wall in the caspase-1 activation, nitric oxide and cytokines production during experimental sporotrichosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a mouse model of systemic infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sporothrix schenckii complex biology: environment and fungal pathogenicity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Antibodies Against Sporothrix schenckii Enhance TNF-a Production and Killing by Macrophages

Sporotrichosis is a chronic granulomatous mycosis caused by the dimorphic fungus Sporothrix schenckii. The immunological mechanisms involved in the prevention and control of sporotrichosis suggest that cell-mediated immunity plays an important role in protecting the host against S. schenckii. Nonetheless, recent data strongly support the existence of protective Abs against this pathogenic fungus. In a previous study, we showed that passive Ab therapy led to a significant reduction in the number of colony forming unit in the organs of mice when the MAb was injected before and during S. schenckii infection. The ability of opsonization to enhance macrophage damage to S. schenckii and subsequent cytokine production was investigated in this work. Here we show that the fungicidal characteristics of macrophages are increased when the fungus is phagocytosed in the presence of inactivated serum from mice infected with S. schenckii or mAb anti-gp70. Additionally, we show an increase in the levels of pro-inflammatory cytokines such as TNF-a and IL-1 beta. This study provides additional support for the importance of antibodies in protecting against S. schenckii and concludes that opsonization is an important process to increase TNF-a production and fungus killing by macrophages in experimental sporotrichosis.

Isolation of Sporothrix schenckii from the claws of domestic cats (indoor and outdoor) and in captivity in São Paulo (Brazil)

Sporotrichosis is a subcutaneous mycosis and is also a zoonosis (sapro- and anthropozoonosis). The objective of the present study was to determine the occurrence of sporotrichosis in domestic cats and in wild or exotic felines in captivity through the isolation of Sporothrix spp. from claw impressions in a culture medium. The samples included 132 felines, of which 120 (91.0 %) were domestic cats, 11 (8.3 %) were wild felines, and one (0.7 %) was an exotic felid. Twenty-one (17.5 %) were outdoor cats. Of the total, 89 (67.4 %) had contact with other animals of the same species. It was possible to isolate Sporothrix schenckii from the claws of one (0.7 %) of the felids probed; this animal exhibited generalised sporotrichosis and had infected a female veterinarian. The potential pathogenic agents Microsporum canis and Malassezia pachydermatis were isolated in 12.1 and 5.3 % of the animals, respectively. The following anemophilous fungi, which were considered to be contaminants, were also isolated: Penicillium sp. (28 or 21.2 %), Aspergillus sp. (13 or 9.8 %), Rhodotorula sp. (5 or 3.8 %), Candida sp. (5 or 3.8 %), Trichoderma sp. (1 or 0.7 %), and Acremonium sp. (1 or 0.7 %). Due to the low magnitude of occurrence (0.7 %) of Sporothrix in feline claws, the potential of the cats evaluated in this study to be sources of infection in the city of São Paulo is considerably low.

Fine-needle aspiration biopsy of disseminated sporotrichosis: A case report

In this report, we describe a case of disseminated sporotrichosis that was diagnosed by fine-needle aspiration biopsy (FNAB). The cytologic smears exhibited a large number of macrophages, few polymorphonuclear neutrophils and numerous round or oval, sometimes elongated, isolated and scattered yeast-like structures localized extracellularly or inside macrophages. These structures were clearly visualized by Giemsa and Papanicolaou methods. Cultures from skin biopsy material revealed,fungal colonies which were subsequently identified as Sporothrix schenckii. The cytologic aspects, the correlation with histologic findings and the differential cytologic diagnosis were reviewed.