Evaluation of the role of tissue repair regulatory T cells during acute and chronic Trypanosoma cruzi infection

S BOCCARDO; CL ARAUJO FURLAN; C RODRIGUEZ; CP ABRATE; L ALMADA; A GRUPPI; CL MONTES; EV ACOSTA RODRÍGUEZ

Congreso; Reunión de Sociedades de Biociencias 2020; 2020

Tissue repair CD4+Foxp3+ regulatory T cells (tisTregs) are a specialized Treg subset that exhibit tissue-specific phenotypic, functional and transcriptional profiles. tisTregs maintain tissue homeostasis and also display conventional immunoregulatory properties. T. cruzi (Tc) triggers a strong effector response that controls parasite spreading but promotes pathological tissue damage. We previously determined that during the acute phase of Tc infection, there is a reduction in tisTregs frequency and numbers in Spleen, Liver and Skeletal Muscle (SM) that correlates with decreased systemic levels of their growth factor IL-33. We also found altered values of biochemical markers of tissue damage (LDH, AST, ALT, CK-MB, glucose) in plasma.In the current work we aimed to evaluate the behavior of this cell population and its correlation with biomarkers of damage as well as systemic IL-33 levels during the chronic phase of this infection. Tothis end, Foxp3-GFP C57BL/6 mice were infected (INF) with 5000 Tc parasites (Tulahuen). At 170 days post infection, (ST2+KLRG-1+) tisTreg cell numbers were quantified at different tissues by flow cytometry. The frequency and numbers of tisTregs were increased in target tissues like skeletal muscle and visceral adipose tissue but not in spleen and liver from INF mice in comparison to non-infected controls. INF mice also showed higher plasma levels of IL-33, as determined by ELISA. Lastly, only an elevated level of LDH among other biochemical markers remained in INF versus NI mice as evidence of damage.This results together with our reported data support the speculation that during the acute phase of Tc infection, the decrease of tisTregs may be necessary to allow the immune control of parasite replication; while their expansion in target tissues during the chronic phase might be necessary to avoid excessive damage over time. Modulation of this cell population would allow us to better understand its role in this disease.