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Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi

BACKGROUND: Trypanosoma cruzi is a protozoan parasite and an etiological agent of Chagas disease. There is a wide variability in the clinical outcome of its infection, ranging from asymptomatic individuals to those with chronic fatal mega syndromes. Both parasite and host factors, as well as their i...

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Autores principales: Arroyo-Olarte, Ruben D, Martínez, Ignacio, Cruz-Rivera, Mayra, Mendlovic, Fela, Espinoza, Bertha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Instituto Oswaldo Cruz, Ministério da Saúde 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851054/
https://www.ncbi.nlm.nih.gov/pubmed/29513875
http://dx.doi.org/10.1590/0074-02760170332
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author Arroyo-Olarte, Ruben D
Martínez, Ignacio
Cruz-Rivera, Mayra
Mendlovic, Fela
Espinoza, Bertha
author_facet Arroyo-Olarte, Ruben D
Martínez, Ignacio
Cruz-Rivera, Mayra
Mendlovic, Fela
Espinoza, Bertha
author_sort Arroyo-Olarte, Ruben D
collection PubMed
description BACKGROUND: Trypanosoma cruzi is a protozoan parasite and an etiological agent of Chagas disease. There is a wide variability in the clinical outcome of its infection, ranging from asymptomatic individuals to those with chronic fatal mega syndromes. Both parasite and host factors, as well as their interplay, are thought to be involved in the process. OBJECTIVES: To evaluate the resistance to complement-mediated killing in two T. cruzi TcI strains with differential virulence and the subsequent effect on their infectivity in mammalian cells. METHODS: Tissue-culture derived trypomastigotes of both strains were incubated in guinea pig serum and subjected to flow cytometry in order to determine their viability and complement activations. Trypomastigotes were also incubated on host cells monolayers in the presence of serum, and infectivity was evaluated under different conditions of complement pathway inhibition. Relative expression of the main parasite-specific complement receptors between the two strains was assessed by quantitative real-time polymerase chain reaction. FINDINGS: In this work, we showed that two TcI strains, one with lower virulence (Ninoa) compared to the other (Qro), differ in their resistance to the lytic activity of complement system, hence causing a compromised ability of Ninoa strain to invade mammalian cells. These results correlate with the three-fold lower messenger RNA (mRNA) levels of complement regulatory protein (CRP), trypomastigote-decay acceleration factor (T-DAF), and complement C2 receptor inhibitor trispanning (CRIT) in Ninoa compared to those in Qro. On the other hand, calreticulin (CRT) mRNA and surface protein levels were higher in Ninoa strain and promoted its infectivity when the lectin pathway of the complement system was inhibited. MAIN CONCLUSIONS: This work suggests the complex interplay of CRP, T-DAF, CRIT, and CRT, and the diagnostic value of mRNA levels in the assessment of virulence potential of T. cruzi strains, particularly when dealing with isolates with similar genetic background.
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spelling pubmed-58510542018-03-20 Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi Arroyo-Olarte, Ruben D Martínez, Ignacio Cruz-Rivera, Mayra Mendlovic, Fela Espinoza, Bertha Mem Inst Oswaldo Cruz Original Article BACKGROUND: Trypanosoma cruzi is a protozoan parasite and an etiological agent of Chagas disease. There is a wide variability in the clinical outcome of its infection, ranging from asymptomatic individuals to those with chronic fatal mega syndromes. Both parasite and host factors, as well as their interplay, are thought to be involved in the process. OBJECTIVES: To evaluate the resistance to complement-mediated killing in two T. cruzi TcI strains with differential virulence and the subsequent effect on their infectivity in mammalian cells. METHODS: Tissue-culture derived trypomastigotes of both strains were incubated in guinea pig serum and subjected to flow cytometry in order to determine their viability and complement activations. Trypomastigotes were also incubated on host cells monolayers in the presence of serum, and infectivity was evaluated under different conditions of complement pathway inhibition. Relative expression of the main parasite-specific complement receptors between the two strains was assessed by quantitative real-time polymerase chain reaction. FINDINGS: In this work, we showed that two TcI strains, one with lower virulence (Ninoa) compared to the other (Qro), differ in their resistance to the lytic activity of complement system, hence causing a compromised ability of Ninoa strain to invade mammalian cells. These results correlate with the three-fold lower messenger RNA (mRNA) levels of complement regulatory protein (CRP), trypomastigote-decay acceleration factor (T-DAF), and complement C2 receptor inhibitor trispanning (CRIT) in Ninoa compared to those in Qro. On the other hand, calreticulin (CRT) mRNA and surface protein levels were higher in Ninoa strain and promoted its infectivity when the lectin pathway of the complement system was inhibited. MAIN CONCLUSIONS: This work suggests the complex interplay of CRP, T-DAF, CRIT, and CRT, and the diagnostic value of mRNA levels in the assessment of virulence potential of T. cruzi strains, particularly when dealing with isolates with similar genetic background. Instituto Oswaldo Cruz, Ministério da Saúde 2018-02-19 /pmc/articles/PMC5851054/ /pubmed/29513875 http://dx.doi.org/10.1590/0074-02760170332 Text en https://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Arroyo-Olarte, Ruben D
Martínez, Ignacio
Cruz-Rivera, Mayra
Mendlovic, Fela
Espinoza, Bertha
Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi
title Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi
title_full Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi
title_fullStr Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi
title_full_unstemmed Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi
title_short Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi
title_sort complement system contributes to modulate the infectivity of susceptible tci strains of trypanosoma cruzi
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851054/
https://www.ncbi.nlm.nih.gov/pubmed/29513875
http://dx.doi.org/10.1590/0074-02760170332
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