TRYPANOSOMA CRUZI PROMOTES MACROPHAGE DEDIFFERENTIATION AND TRANSITION INTO MYOFIBROBLAST-LIKE CELLS.

VOLPINI, XIMENA; QUIROZ, JM; BRUGO, MARIA BELEN; LAVALLEN, JAZMIN; HERRERA, MELISA ROCÍO ; FOZZATTI, LAURA; MUSRI, MELINA; MOTRAN, CLAUDIA

Mar del Plata

Congreso; LXX Reunión Anual de la Sociedad Argentina de Inmunología.; 2022

Dedifferentiation is the process by which cells return from a partially or terminally differentiated stage to a lesser stage of differentiation within their original lineage. Instead, in cell transition, these acquire markers and functions of a different cell lineage from their original. Previously, we have reported macrophage (Mo)-like F4/80+CD11b+ cells expressing α-SMA, a smooth muscle cell, and myofibroblast marker, in the aortas of Trypanosoma cruzi-infected mice. These cells were observed in the media and adventitia layers during the acute and chronic phases of Chagas disease. However, we have not been able to identify the original lineage of these cells. In this work, we aim to study T. cruzi ability to induce Mo dedifferentiation and/or transition. Bone marrow-derived Mo (M0, BMDM) from BALB/c mice were treated in vitro with LPS+IFN-γ or IL-4 to induce M1 or M2 phenotypes respectively, or infected with trypomastigotes of T. cruzi (TC). Also, we used combinations of treatment-plus-infection. We found that TC-infection decreases the frequency of F4/80+CD11b+ cells on M0, M1, and M2 BMDM cultures. In M0 F4/80+CD11b+, TC induced significatively the expression of α-SMA. F4/80+CD-11b+α-SMA+ from TC-infected M0 expressed lower levels of CD45, F4/80, and iNOS while expressed higher levels of CD206, and Arginase- 1 to those M0-controls. Also, TC induced α-SMA expression and increased Arginase-1 levels on M2, while in M1 induced a significant decrease in CD45, F4/80, CD11b, and iNOS levels. Our resultssuggest that TC infection promotes Mo dedifferentiation and transition into myofibroblast-like with possible pro-regenerative functions. Meanwhile, dedifferentiation may be pathological in an infectious context, understanding dedifferentiation mechanisms provides new insights for designing strategies for regenerative medicine. Currently, we are analyzing possible treatments to promote and modulate Mo-dedifferentiation and their tissular pro-regenerative functions