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

BOCCARDO S; ARAUJO FURLÁN CL; RODRIGUEZ C; ABRATE C; ALMADA L; GRUPPI A; MONTES CL; ACOSTA RODRIGUEZ EV

Congreso; Reunión Conjunta SAIC.SAI.AAFE.NANOMED.Ar. 17; 2021

Tissue repair regulatory Foxp3+ CD4+ T cells (trTreg) are a specialized subset thatexhibit tissue-specific phenotypic, functional and transcriptional profiles. trTreg maintaintissue homeostasis and also display conventional immunoregulatory properties. T.cruzi (Tc) triggers a strong effector response that controls parasite spreading butpromotes pathological tissue damage. We previously showed that during the acutephase 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 systemiclevels of their growth factor IL-33 and increased markers of tissue damage. We alsofound 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-GFPC57BL/6 mice infected with 5000 Tc parasites (Tulahuen) were treated on days 12, 15and 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 IL33treatment (Tx) induced a mild expansion of (ST2+KLRG-1+) trTreg in spleen but not inSM, producing no changes on parasite-specific CD8+ T cells or pro/anti-inflammatorymacrophage numbers, total body or SM weights, % of survival, biochemical markers oftissue damage levels and parasitemia. Local IL33 Tx could not increase SM trTregnumbers 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 functionalresponse to IL-33 in these settings. Considering these data, we speculate that acute Tcinfection may induce signals that could counteract IL33 effect on trTreg. Future studieswill be aimed at identifying these signals in order to be able to modulate trTreg and, likely,tissue damage during infection.