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

CONSTANZA RODRIGUEZ; ADRIANA GRUPPI; CINTIA L. ARAUJO FURLAN; LAURA ALMADA; EVA V. ACOSTA RODRIGUEZ; SANTIAGO BOCCARDO; CAROLINA P. ABRATE; CAROLINA L. MONTES

Buenos Aires

Congreso; Reunión Anual de Sociedades de Biociencias - SAIC. SAI. SAFIS. 2020; 2020

SAIC. SAI. SAFIS.

Tissue repair CD4+Foxp3+ regulatory T cells (tisTregs) are a specializedTreg subset that exhibit tissue-specific phenotypic, functionaland transcriptional profiles. tisTregs maintain tissue homeostasisand also display conventional immunoregulatory properties. T.cruzi (Tc) triggers a strong effector response that controls parasitespreading but promotes pathological tissue damage. We previouslydetermined that during the acute phase of Tc infection, there is areduction in tisTregs frequency and numbers in Spleen, Liver andSkeletal Muscle (SM) that correlates with decreased systemic levelsof their growth factor IL-33. We also found altered values of biochemicalmarkers of tissue damage (LDH, AST, ALT, CK-MB, glucose)in plasma.In the current work we aimed to evaluate the behavior of this cellpopulation and its correlation with biomarkers of damage as well assystemic IL-33 levels during the chronic phase of this infection. Tothis end, Foxp3-GFP C57BL/6 mice were infected (INF) with 5000Tc 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 intarget tissues like skeletal muscle and visceral adipose tissue butnot in spleen and liver from INF mice in comparison to non-infectedcontrols. INF mice also showed higher plasma levels of IL-33, asdetermined by ELISA. Lastly, only an elevated level of LDH amongother biochemical markers remained in INF versus NI mice as evidenceof damage.This results together with our reported data support the speculationthat during the acute phase of Tc infection, the decrease of tisTregsmay be necessary to allow the immune control of parasite replication;while their expansion in target tissues during the chronic phasemight be necessary to avoid excessive damage over time. Modulationof this cell population would allow us to better understand itsrole in this disease.