Publication Date
10-25-2023
Journal
Nature Communications
DOI
10.1038/s41467-023-42247-w
PMID
37880260
PMCID
PMC10600178
PubMedCentral® Posted Date
10-25-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Trypanocidal Agents, Chagas Disease, Nitroimidazoles, Heart, Trypanosoma cruzi, Disease Progression
Abstract
Post-infectious conditions present major health burdens but remain poorly understood. In Chagas disease (CD), caused by Trypanosoma cruzi parasites, antiparasitic agents that successfully clear T. cruzi do not always improve clinical outcomes. In this study, we reveal differential small molecule trajectories between cardiac regions during chronic T. cruzi infection, matching with characteristic CD apical aneurysm sites. Incomplete, region-specific, cardiac small molecule restoration is observed in animals treated with the antiparasitic benznidazole. In contrast, superior restoration of the cardiac small molecule profile is observed for a combination treatment of reduced-dose benznidazole plus an immunotherapy, even with less parasite burden reduction. Overall, these results reveal molecular mechanisms of CD treatment based on simultaneous effects on the pathogen and on host small molecule responses, and expand our understanding of clinical treatment failure in CD. This link between infection and subsequent persistent small molecule perturbation broadens our understanding of infectious disease sequelae.
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Biological Phenomena, Cell Phenomena, and Immunity Commons, Cardiology Commons, Diseases Commons, Pediatrics Commons, Tropical Medicine Commons