Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load

Abstract

BackgroundChagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by cardiac, gastrointestinal, and nervous system disorders. Although much about the pathophysiological process of Chagas disease is already known, the influence of the parasite burden on the inflammatory process and disease progression remains uncertain.MethodsWe used an acute experimental disease model to evaluate the effect of T. cruzi on intestinal lesions and assessed correlations between parasite load and inflammation and intestinal injury at 7 and 14 days post-infection. Low (3 × 102), medium (3 × 103), and high (3 × 104) parasite loads were generated by infecting C57BL/6 mice with “Y”-strain trypomastigotes. Statistical analysis was performed using analysis of variance with Tukey’s multiple comparison post-test, Kruskal–Wallis test with Dunn’s multiple comparison, χ2 test and Spearman correlation.ResultsHigh parasite load-bearing mice more rapidly and strongly developed parasitemia. Increased colon width, inflammatory infiltration, myositis, periganglionitis, ganglionitis, pro-inflammatory cytokines (e.g., TNF-α, INF-γ, IL-2, IL-17, IL-6), and intestinal amastigote nests were more pronounced in high parasite load-bearing animals. These results were remarkable because a positive correlation was observed between parasite load, inflammatory infiltrate, amastigote nests, and investigated cytokines.ConclusionsThese experimental data support the idea that the parasite load considerably influences the T. cruzi-induced intestinal inflammatory response and contributes to the development of the digestive form of the disease.

Myenteric neuroprotective role of aspirin in acute and chronic experimental infections with Trypanosoma cruzi

“…This inflammatory process was demonstrated in this study by the presence of inflammatory foci in the colonic wall. Trypanosoma cruzi infected mice usually have intense inflammatory foci in the colonic wall even during the chronic phase of the infection, as we also found in the infected mice treated with PBS. However, we found reduction of the number of inflammatory foci in T. cruzi infected mice treated with ASA during acute or chronic phases.…”

“…We evaluated the level of NO in the colonic tissue since T. cruzi induces upregulation of NO production in several tissues . We observed that the level of NO was reduced in infected mice treated with PBS, possibly due to the intense loss of nitrergic myenteric neurons and also because the inflammatory foci in the colonic wall did not stimulate release of interferon gamma (IFN‐γ).…”

“…The immigration of infected people is responsible for the increasing of cases in non‐Latin American countries, especially by blood transfusion and organ transplants . It is estimated that more than 90 million individuals are currently at risk of infection with the Chagas disease's etiologic agent ( Trypanosoma cruzi ) . The main transmission route is vector borne (triatomine bugs), however, there is also an important concern for the oral transmission route.…”

“…However, there is evidence of selective and partial survival of nitrergic and VIPergic neurons . There is no agreement regarding the cause of myenteric neuron death; however, the most accepted hypothesis is that it is associated with an inflammatory process induced by the presence of the parasite …”

Renal Disfunction in Chagas Disease

“…A study by Lenzi [10] demonstrated the relationship between the disseminated form of infection, tissue damage in the acute phase and the presence of the parasite in the tissue. Other authors have also described the relationship between T. cruzi parasitism and acute infection in other organs, such as the kidney and intestines [11][12][13].…”