GRAIL and Otubain are related to T cell hyporesponsiveness during Trypanosoma cruzi infection

• Autores: Stempin, Cinthia; Rojas Marquez, Jorge David; Ana, Yamile; Cerban, Fabio Marcelo
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: T Cell; T.Cruzi; Grail; Mtor
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Trypanosoma cruzi infection is associated with severe T cell unresponsiveness to antigens and mitogens and is characterized by decreased IL-2 synthesis. On the other hand, acquisition of the anergic phenotype correlated with upregulation of gene related to anergy in lymphocytes (GRAIL) protein in CD4 T cells. We therefore sought to examine the role of GRAIL in CD4 T cell proliferation during T. cruzi infection.Methodology/Principal Findings We sought to examine the role of GRAIL in CD4 T cell proliferation during T. cruzi experimental infection. Balb/c mice were infected intraperitoneally with 500 blood derived trypomastigotes of Tulahuen strain, and spleen cells from control non-infected or infected animals were obtained. CD4 T cell proliferation was assessed by CFSE staining, and the expression of GRAIL in splenic T cells was measured by real-time PCR, flow cytometry and Western blot. We found an increased GRAIL expression at the early stages of infection, coincident with impaired proliferation and poor IL-2 and IFN- secretion in response to plate bound antibodies. In addition, we showed that the expression of GRAIL E3-ubiquitin ligase in CD4+ T cells during the acute phase of infection was complemented by a high expression of inhibitory receptors such as PD-1 and CTL-4. Moreover, we demonstrated that GRAIL expression during infection was regulated by IL-2 since it was able to activate the mammalian target of the rapamycin (mTOR) pathway, inducing Otubain-1 expression that mediated GRAIL degradation and improved T cell proliferation.
Fil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Rojas Marquez, Jorge David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ana, Yamile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cerban, Fabio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina