Increased of α-actin in inflammatory areas following Trypanosoma cruzi infection suggests the onset of megacolon.

The inflammatory process triggered byTrypanosoma cruzi infection plays a central role in the pathogenesis of chagasic megacolon, primarily through enteric nervous system (ENS) damage and intestinal wall remodeling. This study aimed to evaluate histological, morphometric, and immunohistochemical alterations in the colonic muscle layer and enteric glial components during the progression of Chagas disease. Forty-four male Swiss mice were infected with the T. cruzi QM2 strain and analyzed at 60 days (acute phase) and 180 days (chronic phase) post-infection. Histopathological, morphometric, and immunohistochemical analyses were performed to assess inflammatory infiltrate, tissue architecture, collagen deposition, mast cell density, and the expression of S100, GFAP, and alpha-smooth muscle actin (α-SMA) proteins. The acute phase was characterized by intense inflammation, presence of amastigote nests, morphometric alterations, increased GFAP and α-SMA expression, and decreased S100 expression. In the chronic phase, the inflammatory infiltrate persisted, accompanied by significant structural remodeling of the colonic wall, although without fibrosis or changes in mast cell density. Notably, the increased α-SMA expression was strongly associated with the presence of inflammatory infiltrate. These findings provide robust evidence of an early and progressive colonic wall remodeling process, highlighting key cellular and molecular mechanisms involved in the development of digestive manifestations in Chagas disease, and reinforce the relevance of the murine model for investigating the pathophysiology of chagasic megacolon.