Perturbed T cell IL-7 receptor signaling in chronic Chagas disease

• Autores: Albareda, María Cecilia; Pérez-Mazliah, Damián E; Natale, M Ailén; Castro Eiro, Melisa D; Alvarez, María G; Viotti, Rodolfo; Bertocchi, Graciela; Lococo, Bruno; Tarleton, Rick L; Laucella, Susana A.
• Año de publicación: 2015
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Journal of immunology (Baltimore, Md.:1950) 2015;194(8):3883-3889
• Materia: Trypanosoma cruzi; Receptores de Citocinas; Enfermedad de Chagas
• Institución: Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"

Fil: Albareda, María Cecilia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Pérez-Mazliah, Damián E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Natale, M. Ailén. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Castro Eiro, Melisa D. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Alvarez, María G. Hospital Interzonal General de Agudos Eva Perón; Argentina.
Fil: Viotti, Rodolfo. Hospital Interzonal General de Agudos Eva Perón; Argentina.
Fil: Bertocchi, Graciela. Hospital Interzonal General de Agudos Eva Perón; Argentina.
Fil: Lococo, Bruno. Hospital Interzonal General de Agudos Eva Perón; Argentina.
Fil: Tarleton, Rick L. enter for Tropical and Emerging Global Diseases, Athens, Georgia; Estados Unidos.
Fil: Laucella, Susana A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
We have previously demonstrated that immune responses in subjects with chronic Trypanosoma cruzi infection display features common to other persistent infections with signs of T cell exhaustion. Alterations in cytokine receptor signal transduction have emerged as one of the cell-intrinsic mechanisms of T cell exhaustion. In this study, we performed an analysis of the expression of IL-7R components (CD127 and CD132) on CD4(+) and CD8(+) T cells and evaluated IL-7-dependent signaling events in patients at different clinical stages of chronic chagasic heart disease. Subjects with no signs of cardiac disease showed a decrease in CD127(+)CD132(+) cells and a reciprocal gain of CD127(-)CD132(+) in CD8(+) and CD4(+) T cells compared with either patients exhibiting heart enlargement or uninfected controls. T. cruzi infection, in vitro, was able to stimulate the downregulation of CD127 and the upregulation of CD132 on T cells. IL-7-induced phosphorylation of STAT5 as well as Bcl-2 and CD25 expression were lower in T. cruzi-infected subjects compared with uninfected controls. The serum levels of IL-7 were also increased in chronic chagasic patients. The present study highlights perturbed IL-7/IL-7R T cell signaling through STAT5 as a potential mechanism of T cell exhaustion in chronic T. cruzi infection.