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AutorOliveira, Pablo Rafael Silveira
AutorDessein, Hélia
AutorRomano, Audrey
AutorCabantous, Sandrine
AutorBrito, Maria E. F. de
AutorSantoro, Ferrucio
AutorPitta, Maira Galdino da Rocha
AutorPereira, Valéria
AutorPontes-de-Carvalho, Lain Carlos
AutorRodrigues Junior, Virmondes
AutorRafati, Sima
AutorArgiro, Laurent
AutorDessein, Alain J
Fecha de acceso2015-07-15T14:18:03Z
Fecha de disponibilización2015-07-15T14:18:03Z
Fecha de publicación2015
ReferenciaOLIVEIRA, P. R. S. et al. IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis. Journal of Immunology, v. 194, n. 6, p. 2664-2672, 2015.pt_BR
ISSN0022-1767
URIhttps://www.arca.fiocruz.br/handle/icict/11368
Idiomaengpt_BR
EditorAmerican Association of Immunologistspt_BR
Derechos de autoropen accesspt_BR
TítuloIL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.pt_BR
Tipo del documentoArticlept_BR
DOI10.4049/jimmunol.1402047
Resumen en InglésThe outcome of Leishmania infections varies substantially, depending on the host and the parasite strain; infection may be asymptomatic or cause mild or severe skin ulcers (cutaneous leishmaniasis [CL]), limited or disseminated lesions, or lethal visceral disease. We previously reported an association between IL-2R mutations and susceptibility to visceral leishmaniasis in children infected with Leishmania donovani. In the present study, we evaluated the possible role of IL-2 signaling in human CL. We first showed that the transcripts of several genes of the IL-2 pathway were abundant in skin lesions caused by Leishmania braziliensis. We then carried out a genetic analysis, focusing on major genes of the IL-2 pathway. We used a family-based approach and found that polymorphisms of several genes appeared to be associated with CL in a Brazilian population. Moreover, two polymorphisms of the IL2RA gene were significantly and independently associated with CL. We confirmed this result in a second Brazilian sample (also exposed to L. braziliensis) and in Iranians infected with Leishmania tropica: IL2RA rs10905669 T (Pcombined = 6 3 1027) and IL2RA rs706778 T (Pcombined = 2 3 1029) were associated with greater susceptibility to lesion development. These alleles were also correlated with a poor IFN-g response and poor FOXP3+ regulatory T cell activation. Thus, IL-2 plays a crucial role in protection against the cutaneous ulcers caused by Leishmania, and the IL-2 pathway is a potential target for strategies aiming to control Leishmania-related diseases.pt_BR
AfiliaciónAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, Brasilpt_BR
AfiliaciónAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, Francept_BR
AfiliaciónAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, Francept_BR
AfiliaciónAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, Francept_BR
AfiliaciónFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratorio de Imunogenética. Departamento de Imunologia. Recife, PE, Brasilpt_BR
AfiliaciónAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, Francept_BR
AfiliaciónAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, Francept_BR
AfiliaciónFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratorio de Imunogenética. Departamento de Imunologia. Recife, PE, Brasilpt_BR
AfiliaciónFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, Brasilpt_BR
AfiliaciónFederal University of the Triangulo Mineiro. Laboratory of Immunology. Department of Biological Sciences. Uberaba, MG, Brasilpt_BR
AfiliaciónPasteur Institute of Tehran. Laboratory of Immunology. Tehran, Iranpt_BR
AfiliaciónAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, Francept_BR
AfiliaciónAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, Francept_BR
DeCSSubunidade alfa de Receptor de Interleucina-2/imunologiapt_BR
DeCSInterleucina-2/imunologiapt_BR
DeCSLeishmania braziliensis/imunologiapt_BR
DeCSLeishmaniose Cutânea/imunologiapt_BR
DeCSPolimorfismo de Nucleotídeo Único/imunologiapt_BR
DeCSAdolescentept_BR
DeCSAdultopt_BR
DeCSCriançapt_BR
DeCSFemininopt_BR
DeCSFatores de Transcrição Forkhead/imunologiapt_BR
DeCSFatores de Transcrição Forkhead/metabolismopt_BR
DeCSPerfilação da Expressão Gênicapt_BR
DeCSPredisposição Genética para Doença/genéticapt_BR
DeCSGenótipopt_BR
DeCSInterações Hospedeiro-Parasita/imunologiapt_BR
DeCSHumanospt_BR
DeCSInterferon gama/imunologiapt_BR
DeCSSubunidade alfa de Receptor de Interleucina-2/genéticapt_BR
DeCSLeishmania braziliensis/fisiologiapt_BR
DeCSLeishmaniose Cutânea/genéticapt_BR
DeCSDesequilíbrio de Ligaçãopt_BR
DeCSMasculinopt_BR
DeCSMeia-Idadept_BR
DeCSAnálise de Sequência com Séries de Oligonucleotídeospt_BR
DeCSLinfócitos T Reguladores/metabolismopt_BR


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