Journal
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2020.583899
Keywords
Trypanosoma cruzi; pathogenesis; intestinal chagas' s disease; experimental model; nitric oxide (NO); reactive species; nitrergic neurons; enteric nervous system (ENS)
Categories
Funding
- CAPES/Brazil
- CNPq/Brazil [305952/2017]
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais-FAPEMIG/Brazil [PPM 00346-14, 00304-16, CBB-APQ-01419-14, APQ-00921-18]
Ask authors/readers for more resources
There is a growing consensus that the balance between the persistence of infection and the host immune response is crucial for chronification of Chagas heart disease. Extrapolation for chagasic megacolon is hampered because research in humans and animal models that reproduce intestinal pathology is lacking. The parasite-host relationship and its consequence to the disease are not well-known. Our model describes the temporal changes in the mice intestine wall throughout the infection, parasitism, and the development of megacolon. It also presents the consequence of the infection of primary myenteric neurons in culture with Trypanosoma cruzi (T. cruzi). Oxidative neuronal damage, involving reactive nitrogen species induced by parasite infection and cytokine production, results in the denervation of the myenteric ganglia in the acute phase. The long-term inflammation induced by the parasite's DNA causes intramuscular axonal damage, smooth muscle hypertrophy, and inconsistent innervation, affecting contractility. Acute phase neuronal loss may be irreversible. However, the dynamics of the damages revealed herein indicate that neuroprotection interventions in acute and chronic phases may help to eradicate the parasite and control the inflammatory-induced increase of the intestinal wall thickness and axonal loss. Our model is a powerful approach to integrate the acute and chronic events triggered by T. cruzi, leading to megacolon.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available