Effect of Trypanosoma cruzi cytosolic triparedoxin peroxidase on pheripheral blood mononuclear cells from patients with chronic Chagas disease

Abstract

Trypanosoma cruzi, the etiological agent of Chagas disease (ChD), has a highly efficient detoxification system to deal with the oxidative burst imposed by its host. One of the antioxidant enzymes involved is the cytosolic tryparedoxin peroxidase (TcCPx) which catalyzes the reduction of hydrogen peroxide, small-chain organic hydroperoxides and ONOO-. This enzyme is present in all parasite stages, and its over-expression renders parasites more resistant to oxidative defenses of macrophages, indicating an important role in parasite survival. However, TcCPx not only constitutes a relevant virulence factor in ChD, but also promotes inflammatory reactions in T. cruzi-infected mice. The aim of this study was to analyze the specific humoral and cellular immune response triggered by TcCPx in chronic asymptomatic (n=7) and cardiac patients (n=6), and non-infected individuals (n=5). Results showed that levels of IgG antibodies against TcCPx were low (titer<1/400) in sera from individuals across all groups. However, after five days of in vitro stimulation, TcCPx induced proliferation of peripheral blood mononuclear cells (PBMC) from asymptomatic patients (p<0.01). In addition, only interferon-γ, but not GM-CSF or IL-10, were detected in the supernatant of PBMC from asymptomatic patients (p=0.04) under the same culture conditions. No response of either type was observed in cardiac patients and non-infected individuals. NetMHCpan and NetMHCIIpan were used to predict potential binding peptides within TcCPx for HLA-class I and II, respectively. The algorithm highlighted four regions of 16-23 aminoacids long containing peptides with high binding probability to most prevalent alleles of α and β chains of HLA-II in central and Northern Argentine population, while potential HLA-I epitopes were mostly found in N-terminal region of the protein. We expect that our research can contribute to understand the role of TcCPx on the immune response of chronic Chagas disease patients.