IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.

dc.creatorOliveira, Pablo Rafael Silveira
dc.creatorDessein, Hélia
dc.creatorRomano, Audrey
dc.creatorCabantous, Sandrine
dc.creatorBrito, Maria E. F. de
dc.creatorSantoro, Ferrucio
dc.creatorPitta, Maira Galdino da Rocha
dc.creatorPereira, Valéria
dc.creatorPontes-de-Carvalho, Lain Carlos
dc.creatorRodrigues Junior, Virmondes
dc.creatorRafati, Sima
dc.creatorArgiro, Laurent
dc.creatorDessein, Alain J
dc.date2015-07-15T14:18:03Z
dc.date2015-07-15T14:18:03Z
dc.date2015
dc.date.accessioned2023-09-26T21:06:49Z
dc.date.available2023-09-26T21:06:49Z
dc.identifierOLIVEIRA, 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.
dc.identifier0022-1767
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/11368
dc.identifier10.4049/jimmunol.1402047
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8869357
dc.descriptionThe 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Association of Immunologists
dc.rightsopen access
dc.subjectSubunidade alfa de Receptor de Interleucina-2/imunologia
dc.subjectInterleucina-2/imunologia
dc.subjectLeishmania braziliensis/imunologia
dc.subjectLeishmaniose Cutânea/imunologia
dc.subjectPolimorfismo de Nucleotídeo Único/imunologia
dc.subjectAdolescente
dc.subjectAdulto
dc.subjectCriança
dc.subjectFeminino
dc.subjectFatores de Transcrição Forkhead/imunologia
dc.subjectFatores de Transcrição Forkhead/metabolismo
dc.subjectPerfilação da Expressão Gênica
dc.subjectPredisposição Genética para Doença/genética
dc.subjectGenótipo
dc.subjectInterações Hospedeiro-Parasita/imunologia
dc.subjectHumanos
dc.subjectInterferon gama/imunologia
dc.subjectSubunidade alfa de Receptor de Interleucina-2/genética
dc.subjectLeishmania braziliensis/fisiologia
dc.subjectLeishmaniose Cutânea/genética
dc.subjectDesequilíbrio de Ligação
dc.subjectMasculino
dc.subjectMeia-Idade
dc.subjectAnálise de Sequência com Séries de Oligonucleotídeos
dc.subjectLinfócitos T Reguladores/metabolismo
dc.titleIL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
dc.typeArticle


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