Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/11368
Title: IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
Authors: Oliveira, Pablo Rafael Silveira
Dessein, Hélia
Romano, Audrey
Cabantous, Sandrine
Brito, Maria E. F. de
Santoro, Ferrucio
Pitta, Maira Galdino da Rocha
Pereira, Valéria
Pontes-de-Carvalho, Lain Carlos
Rodrigues Junior, Virmondes
Rafati, Sima
Argiro, Laurent
Dessein, Alain J
Affilliation: Aix 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, Brasil
Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France
Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France
Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratorio de Imunogenética. Departamento de Imunologia. Recife, PE, Brasil
Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France
Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratorio de Imunogenética. Departamento de Imunologia. Recife, PE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, Brasil
Federal University of the Triangulo Mineiro. Laboratory of Immunology. Department of Biological Sciences. Uberaba, MG, Brasil
Pasteur Institute of Tehran. Laboratory of Immunology. Tehran, Iran
Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France
Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France
Abstract: The 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.
DeCS: Subunidade alfa de Receptor de Interleucina-2/imunologia
Interleucina-2/imunologia
Leishmania braziliensis/imunologia
Leishmaniose Cutânea/imunologia
Polimorfismo de Nucleotídeo Único/imunologia
Adolescente
Adulto
Criança
Feminino
Fatores de Transcrição Forkhead/imunologia
Fatores de Transcrição Forkhead/metabolismo
Perfilação da Expressão Gênica
Predisposição Genética para Doença/genética
Genótipo
Interações Hospedeiro-Parasita/imunologia
Humanos
Interferon gama/imunologia
Subunidade alfa de Receptor de Interleucina-2/genética
Leishmania braziliensis/fisiologia
Leishmaniose Cutânea/genética
Desequilíbrio de Ligação
Masculino
Meia-Idade
Análise de Sequência com Séries de Oligonucleotídeos
Linfócitos T Reguladores/metabolismo
Issue Date: 2015
Publisher: American Association of Immunologists
Citation: OLIVEIRA, 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.
DOI: 10.4049/jimmunol.1402047
ISSN: 0022-1767
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
Oliveira PRS Il2RA genetic....pdf1.09 MBAdobe PDFView/Open



FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.