PD-L2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection.

DULGERIAN L.1; GARRIDO V.2; STEMPIN C.3; CERBÁN F.4

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2011 vol. 133 p. 29 - 40

0019-2805

The programmed death ligand 1 (PD-L1) and 2 (PD-L2) that bind to the receptor programmed death 1 (PD-1) have been involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. However, there are no reports about the role of these molecules during Trypanosoma cruzi infection. We have studied the role of PD-L1 and PD-L2 in T. cruzi infection and its importance in arginase/inducible nitric oxide synthase (iNOS) balance in the immunomodulatory properties of macrophages (Mo). In this work, we have demonstrated that PD-1/PD-Ls pathway expression is modified during T. cruzi infection on Mos obtained from the peritoneal cavity. Mos from T. cruzi-infected mice suppressed T cells proliferation and it was restored when anti-PD-1 and anti-PD-L1 antibodies were added. Nevertheless, anti-PD-L2 antibody treatment did not re-establish T cell proliferation. PD-L2 blockade on peritoneal cells from infected mice showed an increase in arginase expression and activity and decreased iNOS expression and nitric oxide (NO) production. Additionally, IL-10 production was increased while IFN-g production was diminished in the same cultures. Therefore, parasite proliferation was favored. In contrast, PD-1 and PD-L1 blockage increases iNOS expression and NO production on peritoneal Mos from T. cruzi-infected mice. Besides, PD-L2 knock out (KO) infected mice showed an increased in the parasitemia as well as arginase activity and a reduction in NO production. Taken together, we have demonstrated that PD-L2 is involved in the arginase/iNOS balance during T. cruzi infection having a protective role in the immune response against to the parasite.