Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection

Abstract

Trypanosoma cruzi, the aetiological agent of Chagas disease, 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 (c-TXNPx), which catalyses the reduction to hydrogen peroxide, small-chain organic hydroperoxides and peroxynitrite. This enzyme is present in all parasite stages, and its overexpression renders parasites more resistant to the oxidative defences of macrophages, favouring parasite survival. This work addressed the study of the specific humoral and cellular immune response triggered by c-TXNPx in human natural infection. Thus, sera and peripheral blood mononuclear cells (PBMC) were collected from chronically infected asymptomatic and cardiac patients, and non-infected individuals. Results showed that levels of IgG antibodies against c-TXNPx were low in sera from individuals across all groups. B-cell epitope prediction limited immunogenicity to a few, small regions on the c-TXNPx sequence. At a cellular level, PBMC from asymptomatic and cardiac patients proliferated and secreted interferon-γ after c-TXNPx stimulation, compared with mock control. However, only proliferation was higher in asymptomatic patients compared with cardiac and non-infected individuals. Furthermore, asymptomatic patients showed an enhanced frequency of CD19 CD69 cells upon exposure to c-TXNPx. Overall, our results show that c-TXNPx fails to induce a strong immune response in natural infection, being measurable only in those patients without any clinical symptoms. The low impact of c-TXNPx in the human immune response could be strategic for parasite survival, as it keeps this crucial antioxidant enzyme activity safe from the mechanisms of adaptive immune response.

Trypanosoma cruzi-Infected Human Macrophages Shed Proinflammatory Extracellular Vesicles That Enhance Host-Cell Invasion via Toll-Like Receptor 2

“…In this analysis only six parasite proteins were found in EVs from macrophages infected with T. cruzi i.e., HSP60, tryparedoxin peroxidase, trans-sialidase Group II, flagellar calcium-binding protein, surface protein TolT and paraflagellar rod protein 2 (Lobo et al, 2019). These parasite proteins are involved in the recognition of the parasite by host cells, invasion, the adhesion of host cells, metabolism and the induction of the host immune response (Godsel et al, 1995;Quanquin et al, 1999;Mattos et al, 2014;Urményi et al, 2014;Girard et al, 2018).…”

Ex vivo characterization of Breg cells in patients with chronic Chagas disease

“…The remainder of each sample was used to isolate peripheral blood mononuclear cells (PBMC), as described below. The titer of total anti - T. cruzi IgG antibodies in the plasma of patients was determined as previously described 21 . For parasite load, total DNA was extracted from whole blood aliquots using the High Pure PCR Template Preparation kit (Roche Diagnostics Corp., Indiana, USA), following manufacturer-provided instructions.…”

The cytosolic tryparedoxin peroxidase from Trypanosoma cruzi induces a pro‐inflammatory Th1 immune response in a peroxidatic cysteine‐dependent manner

“…Alternatively, antibody titre from each patient or non‐infected donors was determined by ELISA, as previously described 30 . Data were shown as the serum dilution factor that corresponds to 50% of the maximum response (IC50) calculated by non‐linear, dose–response regression analysis using the GraphPad Prism software 30 …”

“…In fact, the Prx from Toxoplasma gondii modulates the function of macrophages by inhibiting the production of IL‐1β and increasing IL‐10 secretion 28 . In a previous work, we demonstrated that in the context of natural infection, c‐TXNPx induces proliferation but not IFN‐γ secretion from peripheral blood mononuclear cells (PBMC) of patients with chronic Chagas disease without any clinical symptoms, but not in those with cardiac alterations 30 . In view of these results, we speculate that the weak immune response triggered by c‐TXNPx could be an evasion strategy developed by T. cruzi due to parasite‐host coevolution.…”