Abstract

Trypanosoma cruzi causes the lethal Chagas disease, which is endemic in Latin America. Flowers of Moringa oleifera (Moringaceae) express a trypsin inhibitor (MoFTI) whose toxicity to T. cruzi trypomastigotes was previously reported. Here, we studied the effects of MoFTI on the viability of human peripheral blood mononuclear cells (PBMCs) as well as on the production of cytokines and nitric oxide (NO) by T. cruzi-infected PBMCs. Incubation with MoFTI (trypsin inhibitory activity: 62 U/mg) led to lysis of trypomastigotes (LC50 of 43.5 µg/mL) but did not affect the viability of PBMCs when tested at concentrations up to 500 µg/mL. A selectivity index > 11.48 was determined. When T. cruzi-infected PBMCs were treated with MoFTI (43.5 or 87.0 µg/mL), the release of the pro-inflammatory cytokine TNF-α and INF-γ, as well as of NO, was stimulated. The release of the anti-inflammatory cytokine IL-10 also increased. In conclusion, the toxicity to T. cruzi and the production of IL-10 by infected PBMCs treated with MoFTI suggest that this molecule may be able to control parasitemia while regulating the inflammation, preventing the progress of Chagas disease. The data reported here stimulate future investigations concerning the in vivo effects of MoFTI on immune response in Chagas disease.

Highlights

  • The Chagas disease, known as American trypanosomiasis, is an endemic and lethal disease common in Latin America

  • Previous reports have shown that plant compounds can act as immunomodulatory agents, and this can bePrevious interesting from have a therapeutic point of view since, when these modulate the production reports shown that plant compounds can act as agents immunomodulatory agents, and ofthis cytokines and other immune mediators, they can increase body defense against pathogens can be interesting from a therapeutic point of view since, when these agents modulate or the pathological is no direct toxicity to the because of production conditions, of cytokineseven andwhen otherthere immune mediators, they cancausative increase agent body [25]; defense against this, we evaluated the effectconditions, of MoFTI even on the release of is cytokines

  • [25]; by no alterations production observed to negativeor because of Interestingly, this, we evaluated the effectof ofcytokine

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Summary

Introduction

The Chagas disease, known as American trypanosomiasis, is an endemic and lethal disease common in Latin America. It is caused by the protozoan Trypanosoma cruzi and the transmission occurs when vertebrates come in contact with the feces of infected triatomine insects, popularly known as “kissing bugs”. 6 to 7 million people worldwide are infected with T. cruzi [1]. The vector harbors epimastigotes and metacyclic trypomastigotes in its gut, while the blood trypomastigotes and the Antibiotics 2020, 9, 515; doi:10.3390/antibiotics9080515 www.mdpi.com/journal/antibiotics. The life cycle of T. cruzi is complex, comprising several evolutionary forms. The vector harbors epimastigotes and metacyclic trypomastigotes in its gut, while the blood trypomastigotes and the intracellular amastigotes hosts

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