Article
IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
Registro en:
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.
0022-1767
10.4049/jimmunol.1402047
Autor
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
Resumen
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.
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