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

VOLPINI, XIMENA; QUIROZ, JUAN NAHUEL; BRUGO, MARÍA BELEN; LAVALLEN, JAZMIN; HERRERA, MELISA; FOZZATTI, LAURA; MUSRI, M; CLAUDIA MOTRAN

Mar del Plata

Congreso; Reunión anual de Sociedades de Biociencias; 2022

SAI-SAIC-FAIC

Dedifferentiation is the process by which cells return from a partiallywithin their original lineage. Instead, in cell transition, these acquiremarkers 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 myofibroblastmarker, in the aortas of Trypanosoma cruzi-infected mice. Thesecells were observed in the media and adventitia layers during theacute and chronic phases of Chagas disease. However, we have notbeen able to identify the original lineage of these cells. In this work,we aim to study T. cruzi ability to induce Mo dedifferentiation and/ortransition. Bone marrow-derived Mo (M0, BMDM) from BALB/c micewere treated in vitro with LPS+IFN-γ or IL-4 to induce M1 or M2phenotypes respectively, or infected with trypomastigotes of T. cruzi(TC). Also, we used combinations of treatment-plus-infection. Wefound 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 expressionand increased Arginase-1 levels on M2, while in M1 induced a significantdecrease in CD45, F4/80, CD11b, and iNOS levels. Our resultssuggest that TC infection promotes Mo dedifferentiation and transitioninto myofibroblast-like with possible pro-regenerative functions.Meanwhile, dedifferentiation may be pathological in an infectiouscontext, understanding dedifferentiation mechanisms provides newinsights for designing strategies for regenerative medicine. Currently,we are analyzing possible treatments to promote and modulateMo-dedifferentiation and their tissular pro-regenerative functions.