Evaluation of the role of tissue repair Regulatory T cells during acute 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 2021; 2021

SAIC - SAI - AAFE - NANOMED-AR

Tissue repair regulatory Foxp3+ CD4+ T cells (trTreg) are a specializedsubset that exhibit tissue-specific phenotypic, functional andtranscriptional profiles. trTreg maintain tissue homeostasis and alsodisplay conventional immunoregulatory properties. T. cruzi (Tc) triggers a strong effector response that controls parasite spreading butpromotes pathological tissue damage. We previously showed thatduring the acute phase of Tc infection, there is a reduction in trTregfrequency and numbers in Spleen (Sp), Skeletal Muscle (SM) andother tissues that correlates with decreased systemic levels of theirgrowth factor IL-33 and increased markers of tissue damage. Wealso found that trTreg, obtained from infected spleen, can be expandedin-vitro by IL-33.In the current work we aimed to increase trTreg numbers in Sp andSM of acutely infected (INF) mice to evaluate their impact on diseaseprogression. To this end, Foxp3-GFP C57BL/6 mice infectedwith 5000 Tc parasites (Tulahuen) were treated on days 12, 15 and18 post infection (pi) with intraperitoneal or intramuscular injection ofIL-33 or PBS. Sp and SM infiltrate was evaluated by flow cytometryat day 20 pi. Systemic IL33 treatment (Tx) induced a mild expansionof (ST2+KLRG-1+) trTreg in spleen but not in SM, producing nochanges on parasite-specific CD8+ T cells or pro/anti-inflammatorymacrophage numbers, total body or SM weights, % of survival, biochemicalmarkers of tissue damage levels and parasitemia. LocalIL33 Tx could not increase SM trTreg numbers and had no effectson any of the parameters mentioned above. Both Tx could, however,expand ILC2 in INF mice and trTreg in non-INF animals, indicatingfunctional response to IL-33 in these settings.Considering these data, we speculate that acute Tc infection mayinduce signals that could counteract IL33 effect on trTreg. Futurestudies will be aimed at identifying these signals in order to be ableto modulate trTreg and, likely, tissue damage during infection.