Papel da microbiota na infecção intragástrica por Trypanosoma cruzi

Abstract

Oral infection by Trypanosoma cruzi can be caused by consumption of food, beverages, fruits and juices as feces from infected triatomines, prepared in areas where humans have invaded the ecological niche and where the enzootic vector reservoir cycle occurs; direct ingestion of vectors infected by T. cruzi; consumption of food contaminated with urine or marsupial secretions containing T. cruzi metacyclic trypomastigotes; ingestion of raw or undercooked game meat; breastfeeding. Outbreaks of the disease have been reported in the Amazon region, south Brazil and Venezuela. It is known that the interaction between the microbiota, intestinal epithelium and innate and adaptive immune cells in homeostasis favors a dominance of regulatory networks that prevent inflammation or an immune-mediated. We hypothesized that the microbiota helps in the regulation of exacerbated inflammatory response and protection of myenteric plexus neurons during T. cruzi intragastric infection. We observed that germ-free (GF) mice had less parasitemia and mortality when compared to conventional (CV) mice. In addition, they presented less hepato-cellular lesion. When we analyzed the cytokine profile of colon tissue homogenate, we noticed that CV animals did not show increased TNF, IL-12p70 or IL-17 after 21 days of infection, contrary to GF animals. Only during the chronic phase (90 days of infection) we observed an increase in the lebels of inflammatory cytokines in CV animals. However, a maintenance in the concentration of IL-10 in the colon was observed when compared to the acute phase. We have also demonstrated that the microbiota seems to play a fundamental role in the control of bowel inflammation, favoring a better maintenance of the intestinal function evaluated with the intestinal transit, and also some control of neuronal damage in the myenteric plexus after the intragastric infection with T. cruzi. We conclude that the microbiota provides desregulation of the inflammatory response triggered by T. cruzi infection, resulting in increased parasite multiplication, mortality, and liver injury. In contrast, a microbiota helps in the neural protection of the myenteric plexus and in the maintenance of intestinal function.