Gene Related to Anergy in Lymphocytes (GRAIL) and Otubain-1 regulate T cell hyporesponsiveness during Trypanosoma cruzi infection

STEMPIN, CC; ROJAS MARQUEZ, JD; ANA, Y; CERBAN, FM.

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Año: 2017 vol. 11

1935-2735

ackgroundTrypanosoma cruzi infection is associated with severe T cell unresponsiveness to antigens and mitogens and is characterized by decreased IL-2 synthesis. In addition, the acquisition of the anergic phenotype is 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 FindingsBalb/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 increased GRAIL expression at the early stages of infection, coinciding with the peak of parasitemia, with these findings correlating with impaired proliferation and poor IL-2 and