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The NLRP 3 inflammasome contributes to host protection during Sporothrix schenckii infection
Author(s) -
Gonçalves Amanda Costa,
Ferreira Lucas Souza,
Manente Francine Alessandra,
Faria Carolina Maria Quinello Gomes,
Polesi Marisa Campos,
Andrade Cleverton Roberto,
Zamboni Dario Simões,
Carlos Iracilda Zeppone
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12719
Subject(s) - inflammasome , sporotrichosis , pyroptosis , sporothrix schenckii , biology , pyrin domain , caspase 1 , innate immune system , pattern recognition receptor , sporothrix , immune system , microbiology and biotechnology , immunology , acquired immune system , inflammation
Summary Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto . Pattern recognition receptors ( PRR s) recognize and respond to pathogen‐associated molecular patterns ( PAMP s) and shape the following adaptive immune response. A family of PRR s most frequently associated with fungal recognition is the nucleotide‐binding oligomerization domain‐like receptor ( NLR ). After PAMP recognition, NLR family pyrin domain‐containing 3 ( NLRP 3) binds to apoptosis‐associated speck‐like protein containing a caspase recruitment domain ( ASC ) and caspase‐1 to form the NLRP 3 inflammasome. When activated, this complex promotes the maturation of the pro‐inflammatory cytokines interleukin‐1 β ( IL ‐1 β ) and IL ‐18 and cell death through pyroptosis. In this study, we aimed to evaluate the importance of the NLRP 3 inflammasome in the outcome of S. schenckii infection using the following three different knockout ( KO ) mice: NLRP 3 −/− , ASC −/− and caspase‐1 −/− . All KO mice were more susceptible to infection than the wild‐type, suggesting that NLRP 3‐triggered responses contribute to host protection during S. schenckii infection. Furthermore, the NLRP 3 inflammasome appeared to be critical for the ex vivo release of IL ‐1 β , 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 NLRP 3 inflammasome links the innate recognition of S. schenckii to the adaptive immune response, so contributing to protection against this infection.