Evaluation of the immune response against Trypanosoma cruzi cytosolic Tryparedoxin Peroxidase in human natural infection.

GÓMEZ, KARINA A; FERNÁNDEZ, MARISA; ROBELLO, CARLOS; OSSOWSKI MICAELA S; GROSSO, JUAN P; GIRARD, MAGALÍ C; LÓPEZ, LUCÍA; HERNÁNDEZ VÁSQUEZ, YOLANDA; PIÑEYRO M. DOLORES; ACEVEDO, GONZALO R

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2018

0019-2805

Trypanosoma cruzi, the etiological 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 catalyzes the reduction of hydrogen peroxide, small-chain organic hydroperoxides and peroxynitrite. This enzyme is present in all parasite stages, and its over-expression renders parasites more resistant to oxidative defenses of macrophages, favoring 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 chronic 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 and small regions on c-TXNPx sequence. At cellular level, PBMC from asymptomatic and cardiac patients proliferated and secreted Interferon-γ after c-TXNPx stimulation, compared to Mock control. However, only proliferation was higher in asymptomatic patients compared to cardiac and non-infected subjects. 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 little impact of c-TXNPx in human immune response could be strategic for parasite survival, as it keeps this crucial anti-oxidant enzyme activity safe from the mechanisms of adaptive immune response.