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Front. Immunol. | doi: 10.3389/fimmu.2018.00896

Extracellular vesicles shed by Trypanosoma cruzi potentiate infection and elicit lipid body formation and PGE2 production in murine macrophages

Maria Isabel Lovo-Martins1, 2,  Aparecida D. Malvezi2, Bruno Fernando C. Lucchetti2,  Vera Lúcia H. Tatakihara2, Patricia A. Mörking1, Admilton G. Oliveira3, Samuel Goldenberg1,  Pryscilla F. Wowk1* and  Phileno Pinge-Filho2*
  • 1Instituto Carlos Chagas, Fundação Oswaldo Cruz, Brazil
  • 2Departamento de Ciências Patológicas, Universidade Estadual de Londrina, Brazil
  • 3Central de Laboratórios de Pesquisa Multiusuários, Universidade Estadual de Londrina, Brazil

During the onset of Trypanosoma cruzi infection, an effective immune response is necessary to control parasite replication and ensure host survival. Macrophages have a central role in innate immunity, acting as an important trypanocidal cell and triggering the adaptive immune response through antigen presentation and cytokine production. However, T. cruzi displays immune evasion mechanisms that allow infection and replication in macrophages, favoring its chronic persistence. One potential mechanism is the release of T. cruzi strain Y extracellular vesicles (EV Y), which participate in intracellular communication by carrying functional molecules that signal host cells and can modulate the immune response. The present work aimed to evaluate immune modulation by EV Y in C57BL/6 mice, a prototype resistant to infection by T. cruzi strain Y, and the effects of direct EV Y stimulation of macrophages in vitro. EV Y inoculation in mice prior to T. cruzi infection resulted in increased parasitemia, elevated cardiac parasitism, decreased plasma nitric oxide (NO), reduced NO production by spleen cells and modulation of cytokine production, with a reduction in TNF-α in plasma and decreased production of TNF-α and IL-6 by spleen cells from infected animals. In vitro assays using bone marrow-derived macrophages showed that stimulation with EV Y prior to infection by T. cruzi increased the parasite internalization rate and release of infective trypomastigotes by these cells. In this same scenario, EV Y induced lipid body formation and PGE2 production by macrophages even in the absence of T. cruzi. In infected macrophages, EV Y decreased production of PGE2 and cytokines TNF-α and IL-6 24 h after infection. These results suggest that EV Y modulates the host response in favor of the parasite and indicate a role for lipid bodies and PGE2 in immune modulation exerted by extracellular vesicles.

Keywords: extracellular vesicles, lipid bodies, Macrophages, Prostaglandin E2, Trypanosoma cruzi

Received: 01 Feb 2018; Accepted: 11 Apr 2018.

Edited by:

Debora Decote-Ricardo, Universidade Federal Rural do Rio de Janeiro, Brazil

Reviewed by:

Hugo C. Castro-Faria-Neto, Fundação Oswaldo Cruz (Fiocruz), Brazil
Laura N. Cariddi, National University of Río Cuarto, Argentina
Danielle O. Nascimento, Universidade Federal do Rio de Janeiro, Brazil  

Copyright: © 2018 Lovo-Martins, Malvezi, Lucchetti, Tatakihara, Mörking, Oliveira, Goldenberg, Wowk and Pinge-Filho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Pryscilla F. Wowk, Instituto Carlos Chagas, Fundação Oswaldo Cruz, Rua Algacyr Munhoz Mader, 3775, Bloco C, Curitiba, 81350-010, Paraná, Brazil,
Dr. Phileno Pinge-Filho, Universidade Estadual de Londrina, Departamento de Ciências Patológicas, Rodovia Celso Garcia Cid,, PR 445, Km 380, Campus Universitário, Centro de Ciências Biológicas, Londrina, 86057-970, Paraná, Brazil,