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Involvement of Major Components from Sporothrix schenckii Cell Wall in the Caspase-1 Activation, Nitric Oxide and Cytokines Production During Experimental Sporotrichosis

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Abstract

Sporotrichosis is a chronic infection caused by the dimorphic fungus Sporothrix schenckii, involving all layers of skin and the subcutaneous tissue. The role of innate immune toll-like receptors 2 and 4 in the defense against this fungus has been reported, but so far, there were no studies on the effect of cell wall major components over the cytosolic oligo-merization domain (NOD)-like receptors, important regulators of inflammation and responsible for the maturation of IL-1β and IL-18, whose functions are dependents of the caspase-1 activation, that can participate of inflammasome. It was evaluated the percentage of activation of caspase-1, the production of IL-1β, IL-18, IL-17, IFN-γ and nitric oxide in a Balb/c model of S. schenckii infection. It was observed a decreased activity of caspase-1 during the fourth and sixth weeks of infection accompanied by reduced secretion of the cytokines IL-1β, IL-18 and IL-17 and high production of nitric oxide. IFN-γ levels were elevated during the entire time course of infection. This temporal reduction in caspase-1 activity coincides exactly with the reported period of fungal burden associated with a transitory immunosuppression induced by this fungus and detected in similar infection models. These results indicate the importance of interaction between caspase-1, cytokines IL-1β and IL-18 in the host defense against S. schenckii infection, suggesting a participation the inflammasome in this response.

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Abbreviations

EL:

Lipid extract

F1:

Alkali-insoluble fraction

NO:

Nitric oxide

BHI:

Brain heart infusion

PBS:

Phosphate-buffered saline

PECs:

Peritoneal exudate cells

LPS:

Lipopolysaccharide

ELISA:

Enzyme-linked immunosorbent assay

ConA:

Concanavalin A

FLICA:

Carboxyfluorescein

IL:

Interleukin

PRR:

Pattern recognition receptors

NLRs:

NOD-like receptors

PAMP:

Pathogen-associated molecular patterns

ASC:

Protein associated with apoptosis

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Acknowledgments

The authors are grateful to Marisa Campos Polesi Placeres for technical support. This work was supported by grants from the State of Sao Paulo Research Foundation (FAPESP) (Grants No. 2013/03190-5), National Council of Scientific and Technological Development (CNPQ) and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES, Brazil) and Foreigner Visiting Professor Program (Grant 07610130).

Ethical standard

The authors declare that the experiments comply with the laws in force in the country in which they were performed.

Conflict of interest

The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Analyses, Faculty of Pharmaceutical Sciences, São Paulo State University, Rua Expedicionários do Brasil, 1621, Araraquara, São Paulo, 14801-902, Brazil

    Amanda Costa Gonçalves, Danielle Cardoso Geraldo Maia, Lucas Souza Ferreira, Luis Gustavo Silva Monnazzi, Pâmela Alegranci, Marisa Campos Polesi Placeres, Alexander Batista-Duharte & Iracilda Zeppone Carlos

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  1. Amanda Costa Gonçalves
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  2. Danielle Cardoso Geraldo Maia
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  3. Lucas Souza Ferreira
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  4. Luis Gustavo Silva Monnazzi
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  5. Pâmela Alegranci
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  6. Marisa Campos Polesi Placeres
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  8. Iracilda Zeppone Carlos
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Correspondence to Iracilda Zeppone Carlos.

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Gonçalves, A.C., Maia, D.C.G., Ferreira, L.S. et al. Involvement of Major Components from Sporothrix schenckii Cell Wall in the Caspase-1 Activation, Nitric Oxide and Cytokines Production During Experimental Sporotrichosis. Mycopathologia 179, 21–30 (2015). https://doi.org/10.1007/s11046-014-9810-0

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