Human interleukin-36γ plays a crucial role in cytokine induction during Sporothrix brasiliensis and S. schenckii infection in keratinocytes and PBMCs

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorKISCHKEL, Brenda
dc.contributor.authorSANTOS, Jessica C. dos
dc.contributor.authorLOPES-BEZERRA, Leila
dc.contributor.authorTABORDA, Carlos P.
dc.contributor.authorJOOSTEN, Leo A. B.
dc.date.accessioned2024-04-05T19:43:16Z
dc.date.available2024-04-05T19:43:16Z
dc.date.issued2024
dc.description.abstractCytokines of the interleukin (IL)-1 superfamily including the different IL-36 isoforms, have been reported as mediators of acute and chronic inflammation in human skin diseases, such as psoriasis. Here, we demonstrated for the first time that Sporothrix schenckii and S. brasiliensis, the fungi that cause subcutaneous infection sporotrichosis, can induce the expression of IL-36 alpha, IL-36 gamma and IL-36Ra in human keratinocytes and primary peripheral blood mononuclear cells (PBMCs). Specifically, IL-36 gamma was differentially expressed by keratinocytes stimulated with Sporothrix yeasts when compared to the commensal microorganism Staphylococcus epidermidis. The exposure of keratinocytes to 24 h or 7-days culture supernatant of PBMCs stimulated with Sporothrix induced higher IL-36 gamma production compared to direct stimulation of keratinocytes with the live fungus. We identified that IL-36 gamma mRNA expression in keratinocytes is increased in the presence of IL-17, TNF, IL-113 and IL-1 alpha and these cytokines may act synergistically to maintain IL-36 gamma production. Lastly, using a cohort of 164 healthy individuals, we showed that individuals carrying variants of the IL36G gene (rs11690399 and rs11683399) exhibit increased IL-36 gamma production as well as increased innate cytokine production after Sporothrix exposure. Importantly, stimulation of PBMCs with recombinant IL-36 gamma increased the production of IL-113 and IL-6, while IL-36Ra were able to decrease the concentration of these cytokines. Our findings contribute to the understanding of the pathogenesis of sporotrichosis and suggest that IL-36 gamma may be involved in maintaining the cytokine loop that leads to tissue destruction by exacerbating the immune response in sporotrichosis. Of high interest, we present the IL-36 signalling pathway as a potential new therapeutic target.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexScopus
dc.description.indexDimensions
dc.description.indexWoS
dc.description.sponsorshipConselho Nacional de Desen-volvimento Cientfico e Tecnol<acute accent>ogico (CNPq)
dc.description.sponsorshipFAPESP [2016/08730-6]
dc.description.sponsorshipCNPq [420480/2018-8]
dc.identifier.citationMICROBIAL PATHOGENESIS, v.188, article ID 106550, 9p, 2024
dc.identifier.doi10.1016/j.micpath.2024.106550
dc.identifier.eissn1096-1208
dc.identifier.issn0882-4010
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/59261
dc.language.isoeng
dc.publisherACADEMIC PRESS LTD- ELSEVIER SCIENCE LTDeng
dc.relation.ispartofMicrobial Pathogenesis
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTDeng
dc.subjectSporotrichosiseng
dc.subjectCytokineseng
dc.subjectSubcutaneous infectioneng
dc.subjectInflammationeng
dc.subject.wosImmunologyeng
dc.subject.wosMicrobiologyeng
dc.titleHuman interleukin-36γ plays a crucial role in cytokine induction during Sporothrix brasiliensis and S. schenckii infection in keratinocytes and PBMCseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryHolanda
hcfmusp.affiliation.countryisonl
hcfmusp.author.externalKISCHKEL, Brenda:Radboud Univ Med Ctr Radboudumc, Dept Internal Med, Nijmegen, Netherlands; Univ Sao Paulo, Dept Microbiol, Inst Ciencias Biomed, Sao Paulo, Brazil
hcfmusp.author.externalSANTOS, Jessica C. dos:Radboud Univ Med Ctr Radboudumc, Dept Internal Med, Nijmegen, Netherlands
hcfmusp.author.externalLOPES-BEZERRA, Leila:Univ Sao Paulo, Dept Microbiol, Inst Ciencias Biomed, Sao Paulo, Brazil
hcfmusp.author.externalJOOSTEN, Leo A. B.:Radboud Univ Med Ctr Radboudumc, Dept Internal Med, Nijmegen, Netherlands; Iuliu Hatieganu Univ Med & Pharm, Dept Med Genet, Cluj Napoca, Romania; Radboud Univ Nijmegen, Dept Internal Med 463, Med Ctr, Geert Grootepl Zuid 8, NL-6525 GA Nijmegen, Netherlands
hcfmusp.citation.scopus0
hcfmusp.contributor.author-fmusphcCARLOS PELLESCHI TABORDA
hcfmusp.description.articlenumber106550
hcfmusp.description.volume188
hcfmusp.origemWOS
hcfmusp.origem.dimensionspub.1168117878
hcfmusp.origem.pubmed38262494
hcfmusp.origem.scopus2-s2.0-85183997666
hcfmusp.origem.wosWOS:001178117400001
hcfmusp.publisher.cityLONDONeng
hcfmusp.publisher.countryENGLANDeng
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