Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8+ T lymphocytes

Abstract

Trypanosoma cruzi, the etiological agent of Chagas’ disease, may persist for many years in its mammalian host. This suggests escape from the immune response and particularly a suboptimal CD8⁺ T cell response, since these cells are involved in infection control. In this report, we show that T. cruzi inhibits the lipopolysaccharide (LPS)‐induced up‐regulation of MHC class I molecules at the surface of human dendritic cells (DC). To further investigate the functional consequences of this inhibition, a trypomastigote surface antigen‐derived peptide (TSA‐1_514–522 peptide) was selected for its stable binding to HLA‐A*0201 molecules and used to generate a primary T. cruzi‐specific human CD8⁺ T cell line in vitro. We observed that DC infected with T. cruzi or treated with T. cruzi‐conditioned medium (TCM) had a weaker capacity to present this peptide to the specific CD8⁺ T cell line as shown in an IFN‐γ ELISPOT assay. Interestingly, T. cruzi or TCM also reduced the antigen presentation capacity of DC to CD8⁺ T cell lines specific for the influenza virus M_58–66 or HIV RT_476–484 epitopes. This dysfunction appears to be linked essentially to reduced MHC class I molecule expression since the stimulation of the RT_476–484 peptide‐specific CD8⁺ T cell line was shown to depend mainly on the MHC class I–TCR interaction and not on the co‐stimulatory signals which, however, were also inhibited by T. cruzi. This impairment of DC function may represent a novel mechanism reducing in vivo the host’s ability to combat efficiently T. cruzi infection.