Problem
Trypanosoma cruzi and Toxoplasma gondii present, respectively, low and high congenital transmission rates. The placenta as an immune regulatory organ expresses TLRs, leading to the secretion of cytokines. Both parasites are recognized by TLR‐2, TLR‐4, and TLR‐9. Here, we studied if the parasites induce differences in TLR protein expression, cytokine profiles, and whether receptor inhibition is related to parasite infection.
Method of study
Placental tissue explants were infected ex vivo with each parasite, TLRs protein expression, cytokine profile and parasite infection were determined by Western blotting, ELISA and qPCR.
Results
Trypanosoma cruzi and Toxoplasma gondii infection is related to TLR‐2 and TLR‐4/TLR‐9, respectively. Trypanosoma cruzi elicits an increase in TNF‐α, IL‐1β, IL‐6, IL‐8 and IL‐10 cytokine secretion whereas T. gondii only increases the secretion of IL‐8.
Conclusion
The susceptibility of the placenta to each parasite is mediated partially by the innate immune response.
BackgroundChagas disease is caused by Trypanosoma cruzi, a parasite endemic to Latin America. Most infections occur in children by vector or congenital transmission. Trypanosoma cruzi establishes a complexity of specific molecular parasite-host cell interactions to invade the host. However, most studies have been mainly focused on the interaction between the parasite and different cell types, but not on the infection and invasion on a tissue level. During congenital transmission, T. cruzi must cross the placental barrier, composed of epithelial and connective tissues, in order to infect the developing fetus. Here we aimed to study the global changes of transcriptome in the placental tissue after a T. cruzi challenge.ResultsStrong changes in gene expression profiling were found in the different experimental conditions, involving the reprogramming of gene expression in genes involved in the innate immune response.ConclusionsTrypanosoma cruzi induces strong changes in genes involved in a wide range of pathways, especially those involved in immune response against infections.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2988-0) contains supplementary material, which is available to authorized users.
Chagas disease, caused by the protozoan Trypanosoma cruzi, endemic in Latin America but distributed worldwide because of migration. Without appropriate treatment, the disease progresses from an acute asymptomatic phase to a chronic, progressive inflammatory cardiomyopathy causing heart failure and death. Despite specific trypanocidal therapy, heart damage progression cannot be stopped or reversed. Statins, as part of their pleiotropic actions, can modulate chagasic myocarditis by inducing the production of 15-epi-lipoxin A4 (15-epi-LXA4), a proresolution lipid mediator in inflammation. Furthermore, several reports suggest that simvastatin activates the Notch pathway after stroke in cerebral endothelial cells, enhancing blood flow by promoting angiogenesis. Thus, statins are an attractive therapeutic strategy for modulating the Notch pathway to reverse the chronic heart damage induced by T. cruzi. BALB/c mice chronically infected with T. cruzi were treated with 1 mg/kg/day simvastatin or 25 μg/kg/day 15-epi-LXA4 for 20 days. During the treatment period, cardiac function was evaluated by echocardiography. At 80 days postinfection, the heart tissues were assessed for Notch 1 activity. T. cruzi infection activated the Notch 1 pathway, and simvastatin (but not 15-epi-lipoxin A4) produced a further increase in that activity, correlating with improvement in the ejection fraction and histopathologic findings typical of T. cruzi infection, including improvements in inflammation and fibrosis. Moreover, simvastatin increased the number of isolectin B4-positive cells, suggesting active angiogenesis in the chronically infected hearts without alteration of the parasitic load. Simvastatin, probably acting through the Notch 1 pathway, decreases inflammation, improving cardiac function in mice chronically infected with T. cruzi.
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