Bioluminescence imaging of chronic Trypanosoma cruzi infections reveals tissue‐specific parasite dynamics and heart disease in the absence of locally persistent infection

Chronic Trypanosoma cruzi infections lead to cardiomyopathy in 20–30% of cases. A causal link between cardiac infection and pathology has been difficult to establish because of a lack of robust methods to detect scarce, focally distributed parasites within tissues. We developed a highly sensitive bioluminescence imaging system based on T. cruzi expressing a novel luciferase that emits tissue‐penetrating orange‐red light. This enabled long‐term serial evaluation of parasite burdens in individual mice with an in vivo limit of detection of significantly less than 1000 parasites. Parasite distributions during chronic infections were highly focal and spatiotemporally dynamic, but did not localize to the heart. End‐point ex vivo bioluminescence imaging allowed tissue‐specific quantification of parasite loads with minimal sampling bias. During chronic infections, the gastro‐intestinal tract, specifically the colon and stomach, was the only site where T. cruzi infection was consistently observed. Quantitative PCR‐inferred parasite loads correlated with ex vivo bioluminescence and confirmed the gut as the parasite reservoir. Chronically infected mice developed myocarditis and cardiac fibrosis, despite the absence of locally persistent parasites. These data identify the gut as a permissive niche for long‐term T. cruzi infection and show that canonical features of Chagas disease can occur without continual myocardium‐specific infection.