CCL signaling drives T Cell–Macrophage crosstalk in the mouse colon during chronic Trypanosoma cruzi infection

Chagas disease, caused by Trypanosoma cruzi , progresses through acute and chronic phases and is characterized by parasite persistence in multiple tissues, including the heart, gastrointestinal tract, and skeletal muscle. Digestive Chagas disease (DCD) is associated with pathological alterations in the colon during chronic infection. To characterize the immune landscape underlying this process, we used a murine model of chronic DCD and performed single-cell RNA sequencing of colonic lamina propria cells. Our analysis revealed infiltration of T cells, B cells, and macrophages, with T cells representing the predominant immune population in the chronically infected colon. Computational inference of cell-cell communication predicted strong activation of the CCL chemokine signaling pathway, with the CCL5-CCR5 axis emerging as a potential mediator of interactions between CD8 + cytotoxic T cells and macrophages. These findings highlight the importance of chemokine-driven immune coordination in chronic infection and provide a foundation for the identification of biomarkers and the development of targeted therapeutic strategies for chronic DCD.