title: Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a mouse model of systemic infection.
abstract: The discovery of Th17 cells, along with many other Th cell subsets in the recent years, has expanded the Th1/Th2 paradigm that had persisted since its proposition by Mosmann in 1986. Defined by the characteristic expression of the transcription factor retinoic-related orphan receptor γt (RORγt) and production of IL-17A (IL-17), Th17 cells are powerful inducers of tissue inflammation with a recognized role against extracellular bacteria and fungi. Despite this, the interest in their study came from the pivotal role they play in the development and maintenance of major chronic inflammatory conditions such as multiple sclerosis, rheumatoid arthritis and Crohn's disease, hence they have been the target of promising new anti-Th17 therapies. Accordingly, the identification of opportunistic pathogens whose clearance relies on the Th17 response is of huge prophylactic importance. As shown here for the first time, this applies to Sporothrix schenckii, a thermo-dimorphic fungus and the causative agent of sporotrichosis. Our results show that both Th17 and Th1/Th17 mixed cells are developed during the S. schenckii systemic mice infection, which also leads to augmented production of IL-17 and IL-22. Also, by using an antibody-mediated IL-23 depletion model, we further demonstrate that optimal fungal clearance, but not survival, depends on an intact Th17 response.
authors.affiliation: Department of Clinical Analysis, Araraquara's School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, Júlio Mesquita Filho, Rua Expedicionários do Brasil, 1621, Postal Code: 14801-902 Araraquara, SP, Brazil. Electronic address: gigabreath@hotmail.com.
authors.forename: Lucas Souza
authors.initials: LS
authors.lastname: Ferreira
authors.affiliation: Department of Clinical Analysis, Araraquara's School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, Júlio Mesquita Filho, Rua Expedicionários do Brasil, 1621, Postal Code: 14801-902 Araraquara, SP, Brazil. Electronic address: amandacg13@ig.com.br.
authors.forename: Amanda Costa
authors.initials: AC
authors.lastname: Gonçalves
authors.affiliation: Department of Clinical Analysis, Araraquara's School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, Júlio Mesquita Filho, Rua Expedicionários do Brasil, 1621, Postal Code: 14801-902 Araraquara, SP, Brazil. Electronic address: deivysleandro@gmail.com.
authors.forename: Deivys Leandro
authors.initials: DL
authors.lastname: Portuondo
authors.affiliation: Department of Clinical Analysis, Araraquara's School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, Júlio Mesquita Filho, Rua Expedicionários do Brasil, 1621, Postal Code: 14801-902 Araraquara, SP, Brazil. Electronic address: maiadcg@uol.com.br.
authors.forename: Danielle Cardoso Geraldo
authors.initials: DC
authors.lastname: Maia
authors.affiliation: Department of Clinical Analysis, Araraquara's School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, Júlio Mesquita Filho, Rua Expedicionários do Brasil, 1621, Postal Code: 14801-902 Araraquara, SP, Brazil. Electronic address: marisapolesi@yahoo.com.br.
authors.forename: Marisa Campos Polesi
authors.initials: MC
authors.lastname: Placeres
authors.affiliation: Department of Clinical Analysis, Araraquara's School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, Júlio Mesquita Filho, Rua Expedicionários do Brasil, 1621, Postal Code: 14801-902 Araraquara, SP, Brazil. Electronic address: batistaduhartea@gmail.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Batista-Duharte
authors.affiliation: Department of Clinical Analysis, Araraquara's School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, Júlio Mesquita Filho, Rua Expedicionários do Brasil, 1621, Postal Code: 14801-902 Araraquara, SP, Brazil. Electronic address: carlosiz@fcfar.unesp.br.
authors.forename: Iracilda Zeppone
authors.initials: IZ
authors.lastname: Carlos
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000187:drug effects / Q000276:immunology; D007378:Interleukins / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D013175:Sporothrix / Q000276:immunology*; D013174:Sporotrichosis / Q000276:immunology* / Q000628:therapy; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology; D000097043:Interleukin-22
chemical_list: D019138:Antibodies, Blocking; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D000097043:Interleukin-22
keywords: IL-23 depletion; Sporothrix schenckii; Sporotrichosis; Th17 cell; Th17 response