Effect of T. cruzi Cytosolic Tryparedoxin Peroxidase on B cells from patients with Chronic Chagas Disease.

MAGALÍ C. GIRARD; GONZALO ACEVEDO; MICAELA OSSOWSKI; KARINA GÓMEZ

Girona

Workshop; To-B or not to-B: B-cells in health and disease.; 2017

EMBO

Trypanosoma cruzi, the causative agent of Chagas Disease infects about 6 to 7 million people and hundreds of millions are at risk of becoming infected. Chronic infection can progress to cardiomiopathy and/or digestive abnormalities in up to 30% of infected patients (1). The mechanisms underlying the development of these lesions seem to be related with parasite persistence on tissue lesions and the immune response generated by the host (2). The aim of our project is to investigate whether cytosolic Tryparedoxin Peroxidase (TcCPx) participates in the immunopathological processes by targeting B-cell from patients infected with T. cruzi during the chronic phase. TcCPx not only constitutes a relevant virulence factor in Chagas disease, but also promotes inflammatory reactions in T. cruzi-infected mice (3). Furthermore, Leishmania infantum Tryparedoxin is released to the extracellular medium and promotes B cell proliferation and secretion of IL-10 by a mechanism independent of T cell (4). During the early stage of my PhD project, we analyzed the function and phenotype of magnetically purified B cells from PBMCs of two patients and one non-infected individual incubated with T. cruzi lysate and TcCPx. Results revealed a decrease in mature naïve (IgD+CD27-) and an increase in plasma (CD27+CD138+) and memory plasma (CD27+CD138-) B cells only after incubation with TcCPx. No changes in IFN-γ, IL-10 and IL-17 levels were detected in the supernatants of treated B cells. We expect that our research in this field can contribute to understand the role of B cells in the pathology of Chronic Chagas Disease.1. World Health Organization. Chagas disease: control and elimination (Accessed 2017 Jun 14).2. Machado FS et al. (2012) Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease. Semin Immunopathol 34: 753?770. 3. Piñeyro MD, et al (2008) Peroxiredoxins from Trypanosoma cruzi: virulence factors and drug targets for treatment of Chagas disease? Gene 408:45.4. Menezes Cabral S, et al. A Leishmania Infantum Cytosolic Tryparedoxin Activates B Cells to Secrete Interleukin-10 and Specific Immunoglobulin. Immunology 123.4 (2008): 555?565.