title: Involvement of major components from Sporothrix schenckii cell wall in the caspase-1 activation, nitric oxide and cytokines production during experimental sporotrichosis.
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.
authors.affiliation: Department of Clinical Analyses, Faculty of Pharmaceutical Sciences, São Paulo State University, Rua Expedicionários do Brasil, 1621, Araraquara, São Paulo, 14801-902, Brazil.
authors.forename: Amanda Costa
authors.initials: AC
authors.lastname: Gonçalves
authors.forename: Danielle Cardoso Geraldo
authors.initials: DC
authors.lastname: Maia
authors.forename: Lucas Souza
authors.initials: LS
authors.lastname: Ferreira
authors.forename: Luis Gustavo Silva
authors.initials: LG
authors.lastname: Monnazzi
authors.forename: Pâmela
authors.initials: P
authors.lastname: Alegranci
authors.forename: Marisa Campos Polesi
authors.initials: MC
authors.lastname: Placeres
authors.forename: Alexander
authors.initials: A
authors.lastname: Batista-Duharte
authors.forename: Iracilda Zeppone
authors.initials: IZ
authors.lastname: Carlos
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D002473:Cell Wall; D004789:Enzyme Activation; D058847:Inflammasomes / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D012867:Skin / Q000382:microbiology / Q000473:pathology; D013175:Sporothrix / Q000276:immunology*; D013174:Sporotrichosis / Q000276:immunology*
chemical_list: C587672:IL1B protein, mouse; D058847:Inflammasomes; D020381:Interleukin-17; D020382:Interleukin-18; D053583:Interleukin-1beta; D009569:Nitric Oxide; D007371:Interferon-gamma; D020170:Caspase 1