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.
Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
Michael D
MD
Lewis
Amanda
A
Fortes Francisco
Martin C
MC
Taylor
Hollie
H
Burrell-Saward
Alex P
AP
McLatchie
Michael A
MA
Miles
John M
JM
Kelly
D000818:Animals; D014355:Chagas Disease / Q000378:metabolism / Q000469:parasitology* / Q000503:physiopathology*; D005260:Female; D006331:Heart Diseases / Q000378:metabolism / Q000469:parasitology* / Q000503:physiopathology*; D008163:Luminescent Measurements; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D014349:Trypanosoma cruzi / Q000502:physiology*