Our findings establish that PARP1 functions as a transcriptional coregulator of c-Fos and JunB members of the AP1 family to drive the profibrotic/fibrotic response of Mφ, and they offer novel insights into the role of PARP1 in the transcriptional regulation and release of Mφ gelatinases and profibrotic TGF-β in Chagas disease. Here, FOSB is linked to Chagas disease.