The Major Chromoblastomycosis Etiologic Agent Activates the NLRP3 Inflammasome.

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ID: 46141
2017
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Abstract
is the main etiologic agent of chromoblastomycosis (CBM), one of the most prevalent subcutaneous mycosis in tropical and subtropical countries. CBM is a poorly characterized chronic infection that commonly starts after transcutaneous inoculation of conidia and saprophytic hyphae of . Recently, we have shown that unlike conidia, hyphae and muriform cells (the parasitic morphotype) of promotes an intense inflammatory response pattern , which comprises the production of an inflammasome-derived cytokine, IL-1β. Nonetheless, the mechanisms underlying IL-1β production and maturation upon infection and its functional output in the course of CBM remains unknown. We show here that hyphae, differently from conidia, induce IL-1β secretion in both bone marrow-derived dendritic cells and macrophages. Using inhibitors and knockout cells, we demonstrated that the mechanisms underlying IL-1β production by hyphae-infected macrophages were dependent on dectin-1, -2, and -3 receptors and the Syk-NF-kB signaling pathway. Furthermore, promoted a NLRP3-dependent inflammasome activation, which required potassium efflux, reactive oxygen species production, phagolysosomal acidification, and cathepsin B release as triggers. IL-1β processing and release was mediated primarily by caspase-1 and, to a lesser extent, by caspase-8-dependent cleavage. Finally, we showed using a murine CBM model that elicits a NLRP3-regulated IL-1β and interleukin-18 release , but without NLRP3 inflammasome activation interfering in the course of the experimental infection.
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de-castro2017thefrontiers Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors de Castro, Raffael Júnio Araújo;Siqueira, Isaque Medeiros;Jerônimo, Márcio Sousa;Basso, Angelina Maria Moreschi;Veloso Junior, Paulo Henrique de Holanda;Magalhães, Kelly Grace;Leonhardt, Luiza Chaves;de Oliveira, Stephan Alberto Machado;Bürgel, Pedro Henrique;Tavares, Aldo Henrique;Bocca, Anamélia Lorenzetti;
Journal Frontiers in immunology
Year 2017
DOI
10.3389/fimmu.2017.01572
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