Oral Exposure to Phytomonas serpens Attenuates Thrombocytopenia and Leukopenia during Acute Infection with Trypanosoma cruzi

Rosiane V Da Silva,Sueli F Yamada-Ogatta,Leonardo Da Silva Augusto,Phileno Pinge-Filho,Sergio Schenkman,Luiz V Rizzo,Vera Lúcia H Tatakihara,Lucy M Yamauchi,Aparecida D Malvezi,Danielle Kian

doi:10.1371/journal.pone.0068299

Abstract

Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease.

Highlights

The order Kinetoplastida is composed of flagellated unicellular organisms, some of which live in soil or aquatic environments, while others are parasites responsible for severe diseases in humans, animals, and plants [1,2]
We showed that Phytomonas serpens, a tomato parasite from the order Kinetoplastida, shares antigens with T. cruzi [24] but has no TS activity [25]
C57BL/6 mice infected with 56103 blood T. cruzi trypomastigotes developed thrombocytopenia (Figure 1A) and leukopenia (Figure 1B) during the early stages of infection, a transient effect that lasted as long as acute phase of T. cruzi infection remained

Summary

Introduction

The order Kinetoplastida is composed of flagellated unicellular organisms, some of which live in soil or aquatic environments, while others are parasites responsible for severe diseases in humans, animals, and plants [1,2]. The combined number of people infected by Kinetoplastida pathogens is estimated to be over 20 million, resulting in various health problems and more than 100,000 deaths each year. With half a billion people at risk, mostly in tropical and subtropical areas, these parasites represent an important global health problem with associated significant economic burden [3]. The disease affects about 8 million people in Latin America, of whom 30–40% have or will develop neurologic manifestations [7], cardiomyopathy, and/or digestive megasyndromes [8]. The variability in disease outcome has been attributed to host responses and parasite heterogeneity [9]

Methods

Results

Conclusion