Academic Journal
Enteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy
| العنوان: | Enteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy |
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| المؤلفون: | Archie A. Khan, Harry C. Langston, Louis Walsh, Rebecca Roscoe, Shiromani Jayawardhana, Amanda Fortes Francisco, Martin C. Taylor, Conor J. McCann, John M. Kelly, Michael D. Lewis |
| المصدر: | Nature Communications, Vol 15, Iss 1, Pp 1-16 (2024) |
| بيانات النشر: | Nature Portfolio, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Science |
| مصطلحات موضوعية: | Science |
| الوصف: | Abstract Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. There is a lack of evidence on the mechanism of pathogenesis and rationales for treatment. We used a female C3H/HeN mouse model that recapitulates key clinical manifestations to study how infection dynamics shape DCD pathology and the impact of treatment with the front-line, anti-parasitic drug benznidazole. Curative treatment 6 weeks post-infection resulted in sustained recovery of gastrointestinal transit function, whereas treatment failure led to infection relapse and gradual return of DCD symptoms. Neuro/immune gene expression patterns shifted from chronic inflammation to a tissue repair profile after cure, accompanied by increased cellular proliferation, glial cell marker expression and recovery of neuronal density in the myenteric plexus. Delaying treatment until 24 weeks post-infection led to partial reversal of DCD, suggesting the accumulation of permanent tissue damage over the course of chronic infection. Our study shows that murine DCD pathogenesis is sustained by chronic T. cruzi infection and is not an inevitable consequence of acute stage denervation. The risk of irreversible enteric neuromuscular tissue damage and dysfunction developing highlights the importance of prompt diagnosis and treatment. These findings support the concept of treating asymptomatic, T. cruzi-infected individuals with benznidazole to prevent DCD development. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2041-1723 08550484 |
| Relation: | https://doaj.org/toc/2041-1723 |
| DOI: | 10.1038/s41467-024-48749-5 |
| URL الوصول: | https://doaj.org/article/a4a52838d7184b1199e085504845f411 |
| رقم الانضمام: | edsdoj.4a52838d7184b1199e085504845f411 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20411723 08550484 |
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| DOI: | 10.1038/s41467-024-48749-5 |