In situ expression of Th17 immunologic mediators in American cutaneous leishmaniasis caused by Leishmania (V.) braziliensis and Leishmania (L.) amazonensis in the Brazilian Amazon

dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorRODRIGUES, G. F.
dc.contributor.authorALCâNTARA, L. S.
dc.contributor.authorBARROS, J. P. B.
dc.contributor.authorLIMA, A. C. S. de
dc.contributor.authorCAMPOS, M. B.
dc.contributor.authorMORAES, C.
dc.contributor.authorFERREIRA, A. F.
dc.contributor.authorMATTA, V. L. R.
dc.contributor.authorLAURENTI, M. D.
dc.contributor.authorCORBETT, C. E. P.
dc.contributor.authorSILVEIRA, F. T.
dc.contributor.authorGOMES, C. M. C.
dc.date.accessioned2024-03-13T19:57:55Z
dc.date.available2024-03-13T19:57:55Z
dc.date.issued2023
dc.description.abstractAmerican cutaneous leishmaniasis (ACL) presents a wide spectrum of clinical and immunopathological manifestations. In Brazil, Leishmania (L.) amazonensis[La] and Leishmania(V.)braziliensis[Lb] show the highest pathogenic potential for humans causing different clinical forms: localized cutaneous leishmaniasis (LCL : Lb/La), anergic diffuse cutaneous leishmaniasis (ADCL : La) and mucocutaneous leishmaniasis (MCL : Lb). ADCL and MCL are the most severe forms and infection leads to a cellular immune response at the hyposensitivity and hypersensitivity poles. Th17-cells are involved in the ACL pathogenesis, are derived from naïve TCD4+ cells regulated by RORγt, differentiate in presence of IL-6, TGF-β, IL- 1β, IL-23 and express IL-17. Aim of this study was to characterize the cellular immune response mediated by Th17-profile cells through in situ determination of the expression of RORγt, IL-17, IL-6, TGF-β, IL-1β, and IL-23 in the ACL clinical-immunopathological spectrum caused by L.(L.)amazonensis and L.(V.)braziliensis. Biopsies of skin and mucosal lesions from forty patients including ADCL(n=8), LCL[La](n=17), LCL[Lb](n=9) and MCL(n=6), were examined by immunohistochemistry. The immunostained cells density (cells/mm2) was determined in image analysis system using AxionVision 4.8 software (Zeiss). As the disease evolution time (DET) was different among ACL patients, the effect of DET on the expression of immunological markers was evaluated in different clinical forms and histopathological changes, using ANCOVA. Our results showed significantly increased expression of RORγt, IL-17, IL-6, IL-1β and IL-23 in patients with ACL polar forms (ADCL and MCL); higher TGF-β expression was found in ADCL. DET influenced the expression of RORγt and IL-6 in: clinical forms of ACL and in categories of parasitism. DET also affected the production of RORγt, IL-17, IL-6, TGF-β and IL-1β in types of inflammatory infiltrate, evidencing that DET had effect on the expression of Th17 profile cytokines in ACL. Together, the expression of immunological mediators of Th17 profile in the ACL spectrum, as well as the DET effect, demonstrate the participation of this cell lineage in the immunopathogenesis of ACL, mainly in the polar and more severe forms of ACL spectrum. The dubious role played by Th17-cells may favors immune response suppression and parasitic persistence in ADCL, while in MCL it contributes to an exacerbated immune response and parasite scarcity.eng
dc.description.indexPubMed
dc.description.indexScopus
dc.description.indexDimensions
dc.description.sponsorshipLaboratório de Patologia de Moléstias Infecciosas, (LIM - 50 HC-FMUSP)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP, (2014/50315-0, 2019/17957-2)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES, (888.377397/2019-01, 88887.649146/2021-00)
dc.description.sponsorshipUniversidade de São Paulo, USP
dc.identifier.citationFRONTIERS IN TROPICAL DISEASES, v.4, article ID 1067595, p, 2023
dc.identifier.doi10.3389/fitd.2023.1067595
dc.identifier.issn2673-7515
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/58641
dc.language.isoeng
dc.publisherFRONTIERS MEDIA SAeng
dc.relation.ispartofFrontiers in Tropical Diseases
dc.rightsopenAccesseng
dc.rights.holderCopyright FRONTIERS MEDIA SAeng
dc.subjectAmerican cutaneous leishmaniasiseng
dc.subjectcellular immunityeng
dc.subjectimmunohistochemistryeng
dc.subjectleishmania (V.) braziliensiseng
dc.subjectleishmania(L.)amazonensiseng
dc.subjectTh17-cellseng
dc.titleIn situ expression of Th17 immunologic mediators in American cutaneous leishmaniasis caused by Leishmania (V.) braziliensis and Leishmania (L.) amazonensis in the Brazilian Amazoneng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalBARROS, J. P. B.:Departamento de Patologia, Laboratorio de Patologia de Molestias Infecciosas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
hcfmusp.author.externalLIMA, A. C. S. de:Instituto Evandro Chagas, Secretaria de Ciencia, Tecnologia, Inovaçao e Insumos Estrategicos em Saude, Ministerio da Saude, Para, Ananindeua, Brazil
hcfmusp.author.externalCAMPOS, M. B.:Instituto Evandro Chagas, Secretaria de Ciencia, Tecnologia, Inovaçao e Insumos Estrategicos em Saude, Ministerio da Saude, Para, Ananindeua, Brazil
hcfmusp.author.externalMORAES, C.:Faculdade de Saude Publica da Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
hcfmusp.author.externalSILVEIRA, F. T.:Instituto Evandro Chagas, Secretaria de Ciencia, Tecnologia, Inovaçao e Insumos Estrategicos em Saude, Ministerio da Saude, Para, Ananindeua, Brazil, Nucleo de Medicina Tropical, Universidade Federal do Para, Para, Belem, Brazil
hcfmusp.citation.scopus0
hcfmusp.contributor.author-fmusphcGABRIELA FERNANDES RODRIGUES
hcfmusp.contributor.author-fmusphcLARISSA DOS SANTOS ALCANTARA
hcfmusp.contributor.author-fmusphcAUREA FAVERO FERREIRA
hcfmusp.contributor.author-fmusphcVANIA LUCIA RIBEIRO DA MATTA
hcfmusp.contributor.author-fmusphcMARCIA DALASTRA LAURENTI
hcfmusp.contributor.author-fmusphcCARLOS EDUARDO PEREIRA CORBETT
hcfmusp.contributor.author-fmusphcCLAUDIA MARIA DE CASTRO GOMES
hcfmusp.description.articlenumber1067595
hcfmusp.description.volume4
hcfmusp.origemSCOPUS
hcfmusp.origem.dimensionspub.1155294219
hcfmusp.origem.scopus2-s2.0-85183656570
hcfmusp.relation.referenceEspinosa O.A., Serrano M.G., Camargo E.P., Teixeira M.M.G., Shaw J.J., An appraisal of the taxonomy and nomenclature of trypanosomatids presently classified as leishmania and Endotrypanum, Parasitology, 145, 4, (2018)eng
hcfmusp.relation.referenceDados notificados pelos programas nacionais de Leishmanioses/Serviços de vigilância, Disponível Em, 5, (2022)eng
hcfmusp.relation.referenceCampos M.B., De Castro Gomes C.M., de Souza A.A., Lainson R., Corbett C.E., Silveira F.T., In vitro infectivity of species of Leishmania (Viannia) responsible for American cutaneous leishmaniasis, Parasitol Res, 103, 4, (2008)eng
hcfmusp.relation.referenceSilveira F.T., Lainson R., Corbett C.E., Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian brasil – a review, Mem Inst Oswaldo Cruz, 99, 3, (2004)eng
hcfmusp.relation.referenceSilveira F.T., What makes mucosal and anergic diffuse cutaneous leishmaniases clinically and immunopathogically different? A review in Brazil, Trans R Soc Trop Med Hyg, 29, (2019)eng
hcfmusp.relation.referenceCosta J.M.L., Et al., Leishmaniose cutânea difusa (Lcd) no brasil após 60 anos de sua primeira descrição, Gazeta Médica Da Bahia, 79, 3, (2009)eng
hcfmusp.relation.referenceSilveira F.T., Muller S.R., De Souza A.A.A., Lainson R., Gomes C.M.C., Laurenti M.D., Et al., Revisão sobre a patogenia da leishmaniose tegumentar Americana Na amazônia, com Ênfase À doença causada por Leishmania (V.) braziliensis e L. (L.) Amazonensis, Rev Paraense Medicina Pará, 22, pp. 9-20, (2008)eng
hcfmusp.relation.referenceSacks D., Noben-Trauth N., The immunology of susceptibility and resistance to leishmania major in mice, Nat Rev Immunol, 2, (2002)eng
hcfmusp.relation.referenceMaspi N., Abdoli A., Ghaffarifar F., Pro and anti-inflammatory cytokines in cutaneous leishmaniasis: A review, Pathog Glob Health, 110, 6, (2016)eng
hcfmusp.relation.referenceGonzalez Carrion K., Caracterização das alterações histopatológicas e da resposta imune celular em lesões de Pele de pacientes com leishmaniose cutânea no panamá [Tese], (2020)eng
hcfmusp.relation.referenceGoncalves-De-Albuquerque S., Pessoa-E-Silva R., Trajano-Silva L., De Goes T., De Morais R., Da C Oliveira C., Et al., The equivocal role of Th17 cells and neutrophils on immunopathogenesis of leishmaniasis, Front Immunol, 8, (2017)eng
hcfmusp.relation.referenceCastro G., Liu X., Ngo K., De Leon-Tabaldo A., Zhao S., Luna-Roman R., Et al., Rorγt and rorα signature genes in human Th17 cells, PloS One, 12, 8, (2017)eng
hcfmusp.relation.referenceDong C., Th17 cells in development: An updated view of their molecular identity and genetic programming, Nat Rev Immunol, 8, 5, (2008)eng
hcfmusp.relation.referenceDong C., Differentiation and function of pro-inflammatory Th17 cells, Microbes Infect, 11, 5, (2009)eng
hcfmusp.relation.referencePeters A., Lee Y., Kuchroo V., The many faces of Th17 cells, Curr Opin Immunol, 23, 6, (2011)eng
hcfmusp.relation.referenceVeldhoen M., Hocking R., Atkins C., Locksley R., Stockinger B., Tgf beta in the context of an inflammatory cytokine milieu supports De Novo differentiation of il-17-Producing T cells, Immunity, 24, 2, (2006)eng
hcfmusp.relation.referenceGhoreschi K., Laurence A., Yang X.P., Tato C.M., McGeachy M.J., Konkel J.E., Et al., Generation of pathogenic Th17 cells in the absence of TGF-β signalling, Nature, 467, 7318, (2010)eng
hcfmusp.relation.referenceJin W., Dong C., Il-17 cytokines in immunity and inflammation, Emerg Microbes Infect, 2, 9, (2013)eng
hcfmusp.relation.referenceEspir T., Figueira L.P., Naiff M.F., Da Costa A., Ramalho-Ortigao M., Malheiro A., Et al., Role of inflammatory, anti-inflammatory, and regulatory cytokines in patients infected with cutaneous leishmaniasis in Amazonas state, Brazil, The J Immunol Res, 2014, (2014)eng
hcfmusp.relation.referenceBacellar O., Faria D., Nascimento M., Cardoso T., Gollob K., Dutra W., Et al., Interleukin 17 production among patients with American cutaneous leishmaniasis, J Infect Dis, 200, 1, (2009)eng
hcfmusp.relation.referenceMartins V., Silva F., Caixeta F., Carneiro M., Go-es G., Torres L., Et al., Obesity impairs resistance to leishmania major infection in C57bl/6 mice, PloS Negl Trop Dis, 14, 1, (2020)eng
hcfmusp.relation.referenceSousa L., Carneiro M., Resende M., Martins L., Dos Santos L., Vaz L., Et al., Neutrophils have a protective role during early stages of Leishmania amazonensis infection in Balb/C mice, Parasite Immunol, 36, 1, pp. 13-31, (2014)eng
hcfmusp.relation.referenceShen J., Sun X., Pan B., Cao S., Cao J., Che D., Et al., Il-17 induces macrophages to M2-like phenotype Via nf-κb, Cancer Manag Res, 10, (2018)eng
hcfmusp.relation.referenceGraca G., Volpini A., Romero G., Oliveira Neto M., Hueb M., Porrozzi R., Et al., Development and validation of pcr-based assays for diagnosis of American cutaneous leishmaniasis and identification of the parasite species, Mem Inst Oswaldo Cruz, 107, 5, (2012)eng
hcfmusp.relation.referenceMenezes J., Expressão de Foxp3, il-17 e il-23 Na leishmaniose tegumentar Americana causada por Leishmania (Leishmania) amazonensis e Leishmania (Viannia) braziliensis, Dissertação (Mestrado), (2013)eng
hcfmusp.relation.referenceFlores G., Sandoval Pacheco C., Sosa Ochoa W., Gomes C., Zuniga C., Corbett C., Et al., Th17 lymphocytes in atypical cutaneous leishmaniasis caused by Leishmania L. Infantum Chagasi in central America, Parasite Immunol, 42, 11, (2020)eng
hcfmusp.relation.referenceGonzalez K., Calzada J., Corbett C., Saldana A., Laurenti M., Involvement of the inflammasome and Th17 cells in skin lesions of human cutaneous leishmaniasis caused by Leishmania (Viannia) panamensis, Mediators Inflamm, 27, (2020)eng
hcfmusp.relation.referenceLaurenti M., Sosa-Ochoa W., Araujo Flores G., Sandoval Pacheco C., Tomokane T., Oliveira L., Et al., Evaluation of systemic immunity in atypical cutaneous leishmaniasis caused by Leishmania (L.) Infantum Chagasi, Parasite Immunol, 44, 1-2, (2022)eng
hcfmusp.relation.referenceBoaventura V., Santos C., Cardoso C., De Andrade J., Dos Santos W., Clarencio J., Et al., Human mucosal leishmaniasis: Neutrophils infiltrate areas of tissue damage that express high levels of Th17-related cytokines, Eur J Immunol, 40, 10, (2010)eng
hcfmusp.relation.referenceCosta D., Rocha R., Carvalho R., Lima-Neto A., Harhay M., Costa C., Et al., Serum cytokines associated with severity and complications of kala- azar, Pathog Glob Health, 107, 2, pp. 78-87, (2013)eng
hcfmusp.relation.referenceSandoval Pacheco C., Araujo Flores G., Gonzalez K., De Castro Gomes C., Passero L., Tomokane T., Et al., Macrophage polarization in the skin lesion caused by Neotropical species of Leishmania sp, J Immunol Res, 2021, (2021)eng
hcfmusp.relation.referenceCarneiro F., De Magalhaes A., De Jesus Abreu Almeida Couto M., Bocca A., Muniz-Junqueira M., Ribeiro Sampaio R., Foxp3 expression in lesions of the different clinical forms of American tegumentary leishmaniasis, Parasite Immunol, 31, 10, (2009)eng
hcfmusp.relation.referenceFernandez-Figueroa E., Rangel-Escareno C., Espinosa-Mateos V., Carrillo-Sanchez K., Salaiza-Suazo N., Carrada-Figueroa G., Et al., Disease severity in patients infected with Leishmania mexicana relates to IL-1β, PloS Negl Trop Dos, 6, 5, (2012)eng
hcfmusp.relation.referenceNovais F., Carvalho A., Clark M., Carvalho L., Beiting D., Brodsky I., Et al., Cd8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and il-1β production, PloS Pathog, 13, 2, (2017)eng
hcfmusp.relation.referenceSaha A., Souravi R., Ukil A., Cytokines and signaling networks regulating disease outcomes in leishmaniasis, Infect Immun, 90, 8, (2022)eng
hcfmusp.relation.referenceGomes A.H.S., Martines R.B., Kanamura C.T., Barbo M., Iglezias S.D., Lindoso J.A.L., Et al., American Cutaneous leishmaniasis: In situ imune response of patients with recent and late lesions, Parasite Immunol, 39, 4, (2017)eng
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