Author | Oliveira, Pablo Rafael Silveira | |
Author | Dessein, Hélia | |
Author | Romano, Audrey | |
Author | Cabantous, Sandrine | |
Author | Brito, Maria E. F. de | |
Author | Santoro, Ferrucio | |
Author | Pitta, Maira Galdino da Rocha | |
Author | Pereira, Valéria | |
Author | Pontes-de-Carvalho, Lain Carlos | |
Author | Rodrigues Junior, Virmondes | |
Author | Rafati, Sima | |
Author | Argiro, Laurent | |
Author | Dessein, Alain J | |
Access date | 2015-07-15T14:18:03Z | |
Available date | 2015-07-15T14:18:03Z | |
Document date | 2015 | |
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. | pt_BR |
ISSN | 0022-1767 | |
URI | https://www.arca.fiocruz.br/handle/icict/11368 | |
Language | eng | pt_BR |
Publisher | American Association of Immunologists | pt_BR |
Rights | open access | pt_BR |
Title | IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis. | pt_BR |
Type | Article | pt_BR |
DOI | 10.4049/jimmunol.1402047 | |
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. | pt_BR |
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 | pt_BR |
Affilliation | Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France | pt_BR |
Affilliation | Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France | pt_BR |
Affilliation | Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratorio de Imunogenética. Departamento de Imunologia. Recife, PE, Brasil | pt_BR |
Affilliation | Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France | pt_BR |
Affilliation | Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratorio de Imunogenética. Departamento de Imunologia. Recife, PE, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, Brasil | pt_BR |
Affilliation | Federal University of the Triangulo Mineiro. Laboratory of Immunology. Department of Biological Sciences. Uberaba, MG, Brasil | pt_BR |
Affilliation | Pasteur Institute of Tehran. Laboratory of Immunology. Tehran, Iran | pt_BR |
Affilliation | Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France | pt_BR |
Affilliation | Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France | pt_BR |
DeCS | Subunidade alfa de Receptor de Interleucina-2/imunologia | pt_BR |
DeCS | Interleucina-2/imunologia | pt_BR |
DeCS | Leishmania braziliensis/imunologia | pt_BR |
DeCS | Leishmaniose Cutânea/imunologia | pt_BR |
DeCS | Polimorfismo de Nucleotídeo Único/imunologia | pt_BR |
DeCS | Adolescente | pt_BR |
DeCS | Adulto | pt_BR |
DeCS | Criança | pt_BR |
DeCS | Feminino | pt_BR |
DeCS | Fatores de Transcrição Forkhead/imunologia | pt_BR |
DeCS | Fatores de Transcrição Forkhead/metabolismo | pt_BR |
DeCS | Perfilação da Expressão Gênica | pt_BR |
DeCS | Predisposição Genética para Doença/genética | pt_BR |
DeCS | Genótipo | pt_BR |
DeCS | Interações Hospedeiro-Parasita/imunologia | pt_BR |
DeCS | Humanos | pt_BR |
DeCS | Interferon gama/imunologia | pt_BR |
DeCS | Subunidade alfa de Receptor de Interleucina-2/genética | pt_BR |
DeCS | Leishmania braziliensis/fisiologia | pt_BR |
DeCS | Leishmaniose Cutânea/genética | pt_BR |
DeCS | Desequilíbrio de Ligação | pt_BR |
DeCS | Masculino | pt_BR |
DeCS | Meia-Idade | pt_BR |
DeCS | Análise de Sequência com Séries de Oligonucleotídeos | pt_BR |
DeCS | Linfócitos T Reguladores/metabolismo | pt_BR |