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dc.contributor.authorSouza, Camila O. S.
dc.contributor.authorKetelut-Carneiro, Natalia
dc.contributor.authorMilanezi, Cristiane M.
dc.contributor.authorFaccioli, Lucia H.
dc.contributor.authorGardinassi, Luiz G.
dc.contributor.authorSilva, Joao S.
dc.date2022-08-11T08:10:00.000
dc.date.accessioned2022-08-23T16:51:51Z
dc.date.available2022-08-23T16:51:51Z
dc.date.issued2021-05-18
dc.date.submitted2021-09-21
dc.identifier.citation<p>Souza COS, Ketelut-Carneiro N, Milanezi CM, Faccioli LH, Gardinassi LG, Silva JS. NLRC4 inhibits NLRP3 inflammasome and abrogates effective antifungal CD8<sup>+</sup> T cell responses. iScience. 2021 May 18;24(6):102548. doi: 10.1016/j.isci.2021.102548. PMID: 34142053; PMCID: PMC8184506. <a href="https://doi.org/10.1016/j.isci.2021.102548">Link to article on publisher's site</a></p>
dc.identifier.issn2589-0042 (Linking)
dc.identifier.doi10.1016/j.isci.2021.102548
dc.identifier.pmid34142053
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41938
dc.description.abstractThe recognition of fungi by intracellular NOD-like receptors (NLRs) induces inflammasome assembly and activation. Although the NLRC4 inflammasome has been extensively studied in bacterial infections, its role during fungal infections is unclear. Paracoccidioidomycosis (PCM) is a pathogenic fungal disease caused by Paracoccidioides brasiliensis. Here, we show that NLRC4 confers susceptibility to experimental PCM by regulating NLRP3-dependent cytokine production and thus protective effector mechanisms. Early after infection, NLRC4 suppresses prostaglandin E2 production, and consequently reduces interleukin (IL)-1beta release by macrophages and dendritic cells in the lungs. IL-1beta is required to control fungal replication via induction of the nitric oxide synthase 2 (NOS2) pathway. At a later stage of the disease, NLRC4 impacts IL-18 release, dampening robust CD8(+)IFN-gamma(+) T cell responses and enhancing mortality of mice. These findings demonstrate that NLRC4 promotes disease by regulating the production of inflammatory cytokines and cellular responses that depend on the NLRP3 inflammasome activity.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=34142053&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright 2021 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectImmunology
dc.subjectMycology
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBacterial Infections and Mycoses
dc.subjectFungi
dc.subjectImmunology and Infectious Disease
dc.titleNLRC4 inhibits NLRP3 inflammasome and abrogates effective antifungal CD8(+) T cell responses
dc.typeJournal Article
dc.source.journaltitleiScience
dc.source.volume24
dc.source.issue6
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5775&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4742
dc.identifier.contextkey25048801
refterms.dateFOA2022-08-23T16:51:51Z
html.description.abstract<p>The recognition of fungi by intracellular NOD-like receptors (NLRs) induces inflammasome assembly and activation. Although the NLRC4 inflammasome has been extensively studied in bacterial infections, its role during fungal infections is unclear. Paracoccidioidomycosis (PCM) is a pathogenic fungal disease caused by Paracoccidioides brasiliensis. Here, we show that NLRC4 confers susceptibility to experimental PCM by regulating NLRP3-dependent cytokine production and thus protective effector mechanisms. Early after infection, NLRC4 suppresses prostaglandin E2 production, and consequently reduces interleukin (IL)-1beta release by macrophages and dendritic cells in the lungs. IL-1beta is required to control fungal replication via induction of the nitric oxide synthase 2 (NOS2) pathway. At a later stage of the disease, NLRC4 impacts IL-18 release, dampening robust CD8(+)IFN-gamma(+) T cell responses and enhancing mortality of mice. These findings demonstrate that NLRC4 promotes disease by regulating the production of inflammatory cytokines and cellular responses that depend on the NLRP3 inflammasome activity.</p>
dc.identifier.submissionpathoapubs/4742
dc.contributor.departmentProgram in Innate Immunity, Department of Medicine
dc.source.pages102548


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Copyright 2021 The Authors.  This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2021 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).