title: The NLRP3 inflammasome contributes to host protection during Sporothrix schenckii infection.
abstract: Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto. Pattern recognition receptors (PRRs) recognize and respond to pathogen-associated molecular patterns (PAMPs) and shape the following adaptive immune response. A family of PRRs most frequently associated with fungal recognition is the nucleotide-binding oligomerization domain-like receptor (NLR). After PAMP recognition, NLR family pyrin domain-containing 3 (NLRP3) binds to apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 to form the NLRP3 inflammasome. When activated, this complex promotes the maturation of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and cell death through pyroptosis. In this study, we aimed to evaluate the importance of the NLRP3 inflammasome in the outcome of S. schenckii infection using the following three different knockout (KO) mice: NLRP3-/-, ASC-/-and caspase-1-/-. All KO mice were more susceptible to infection than the wild-type, suggesting that NLRP3-triggered responses contribute to host protection during S. schenckii infection. Furthermore, the NLRP3 inflammasome appeared to be critical for the ex vivo release of IL-1β, IL-18 and IL-17 but not interferon-γ. Additionally, a role for the inflammasome in shaping the adaptive immune response was suggested by the lower frequencies of type 17 helper T (Th17) cells and Th1/Th17 but not Th1 cells in S. schenckii-infected KO mice. Overall, our results indicate that the NLRP3 inflammasome links the innate recognition of S. schenckii to the adaptive immune response, so contributing to protection against this infection.
authors.affiliation: Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University (FCF/UNESP), Araraquara, Brazil.
authors.forename: Amanda Costa
authors.initials: AC
authors.lastname: Gonçalves
authors.affiliation: Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University (FCF/UNESP), Araraquara, Brazil.
authors.forename: Lucas Souza
authors.initials: LS
authors.lastname: Ferreira
authors.affiliation: Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University (FCF/UNESP), Araraquara, Brazil.
authors.forename: Francine Alessandra
authors.initials: FA
authors.lastname: Manente
authors.affiliation: Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University (FCF/UNESP), Araraquara, Brazil.
authors.forename: Carolina Maria Quinello Gomes
authors.initials: CMQG
authors.lastname: de Faria
authors.affiliation: Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University (FCF/UNESP), Araraquara, Brazil.
authors.forename: Marisa Campos
authors.initials: MC
authors.lastname: Polesi
authors.affiliation: Department of Physiology and Pathology, Faculty of Dentistry of Araraquara, São Paulo State University (FOAR/UNESP), Araraquara, Brazil.
authors.forename: Cleverton Roberto
authors.initials: CR
authors.lastname: de Andrade
authors.affiliation: Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo (FMRP/USP), Ribeirão Preto, Brazil.
authors.forename: Dario Simões
authors.initials: DS
authors.lastname: Zamboni
authors.affiliation: Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University (FCF/UNESP), Araraquara, Brazil.
authors.forename: Iracilda Zeppone
authors.identifier: 0000-0002-0084-3468
authors.initials: IZ
authors.lastname: Carlos
mesh_terms: D000818:Animals; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000172:deficiency / Q000378:metabolism*; D013175:Sporothrix / Q000166:cytology / Q000276:immunology*; D013174:Sporotrichosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse
keywords: 
  Sporothrix schenckii
  ; NOD-like receptor family pyrin domain-containing 3 inflammasome; pyroptosis; sporotrichosis