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

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

Congreso; Reunión Conjunta SAIC SAI AAFE NANOMED.AR; 2021

SAIC SAI AAFE NANOMED.AR

Tissue repair regulatory Foxp3+ CD4+ T cells (trTreg) are a specialized subset that exhibit tissue-specific phenotypic, functional and transcriptional profiles. trTreg 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 showed that during the acute phase of Tc infection, there is a reduction in trTreg frequency and numbers in Spleen (Sp), Skeletal Muscle (SM) and other tissues that correlates with decreased systemic levels of their growth factor IL-33 and increased markers of tissue damage. We also found that trTreg, obtained from infected spleen, can be expanded in-vitro by IL-33.In the current work we aimed to increase trTreg numbers in Sp and SM of acutely infected (INF) mice to evaluate their impact on disease progression. To this end, Foxp3-GFP C57BL/6 mice infected with 5000 Tc parasites (Tulahuen) were treated on days 12, 15 and 18 post infection (pi) with intraperitoneal or intramuscular injection of IL-33 or PBS. Sp and SM infiltrate was evaluated by flow cytometry at day 20 pi. Systemic IL33 treatment (Tx) induced a mild expansion of (ST2+KLRG-1+) trTreg in spleen but not in SM, producing no changes on parasite-specific CD8+ T cells or pro/anti-inflammatory macrophage numbers, total body or SM weights, % of survival, biochemical markers of tissue damage levels and parasitemia. Local IL33 Tx could not increase SM trTreg numbers and had no effects on any of the parameters mentioned above. Both Tx could, however, expand ILC2 in INF mice and trTreg in non-INF animals, indicating functional response to IL-33 in these settings. Considering these data, we speculate that acute Tc infection may induce signals that could counteract IL33 effect on trTreg. Future studies will be aimed at identifying these signals in order to be able to modulate trTreg and, likely, tissue damage during infection.