Abstract
SummaryChronic 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.
Highlights
A wide variety of pathogens establish persistent infections by continually evading host immune-mediated clearance and often cause chronic debilitating or fatal illnesses as a consequence
Chronic Trypanosoma cruzi infections lead to cardiomyopathy in 20–30% of cases
We developed a highly sensitive bioluminescence imaging system based on T. cruzi expressing a novel luciferase that emits tissue-penetrating orange-red light
Summary
A wide variety of pathogens establish persistent infections by continually evading host immune-mediated clearance and often cause chronic debilitating or fatal illnesses as a consequence. The strategies that microbes employ to ensure their long-term survival within mammalian hosts include antigenic variation, establishment of sites of latency and direct immunomodulation. The protozoan parasite Trypanosoma cruzi is an important zoonotic pathogen which establishes life-long infection in humans and causes Chagas disease (American trypanosomiasis). At least 8 million people in Latin America are estimated to be infected with T. cruzi, resulting in ∼ 13 000 deaths annually and a significant morbidity burden (Moncayo and Silveira, 2009). Recent estimates indicate there are 300 000 infected people living in the USA (Bern and Montgomery, 2009) and up to 123 000 in Europe (Basile et al, 2011). Transmission is primarily mediated by triatomine bug vectors but the congenital route, consumption of contaminated food and drink, organ transplantation and blood transfusion are all important additional infection risks (Marin-Neto et al, 2008)
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