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The Impact of the CTHRSSVVC Peptide Upon Experimental Models of Trypanosoma cruzi Infection

Chagas disease (CD), caused by the hemoflagellate protozoan Trypanosoma cruzi, affects more than six million people worldwide and presents an unsatisfactory therapy, based on two nitroderivatives, introduced in clinical medicine for decades. The synthetic peptide, with CTHRSSVVC sequence (PepA), mim...

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Autores principales: Leite, Gabriela Rodrigues, Batista, Denise da Gama Jaén, Mazzeti, Ana Lia, Silva, Rosemeire Aparecida, Lugão, Ademar Benévolo, Soeiro, Maria de Nazaré Correia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121062/
https://www.ncbi.nlm.nih.gov/pubmed/35601101
http://dx.doi.org/10.3389/fcimb.2022.882555
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author Leite, Gabriela Rodrigues
Batista, Denise da Gama Jaén
Mazzeti, Ana Lia
Silva, Rosemeire Aparecida
Lugão, Ademar Benévolo
Soeiro, Maria de Nazaré Correia
author_facet Leite, Gabriela Rodrigues
Batista, Denise da Gama Jaén
Mazzeti, Ana Lia
Silva, Rosemeire Aparecida
Lugão, Ademar Benévolo
Soeiro, Maria de Nazaré Correia
author_sort Leite, Gabriela Rodrigues
collection PubMed
description Chagas disease (CD), caused by the hemoflagellate protozoan Trypanosoma cruzi, affects more than six million people worldwide and presents an unsatisfactory therapy, based on two nitroderivatives, introduced in clinical medicine for decades. The synthetic peptide, with CTHRSSVVC sequence (PepA), mimics the CD163 and TNF-α tripeptide “RSS” motif and binds to atheromatous plaques in carotid biopsies of human patients, spleen tissues, and a low-density lipoprotein receptor knockout (LDLr−/−) mouse model of atherosclerosis. CD163 receptor is present on monocytes, macrophages, and neutrophils, acting as a regulator of acute-phase processes and modulating aspects of the inflammatory response and the establishment of infections. Due to the potential theranostic role of PepA, our aim was to investigate its effect upon T. cruzi infection in vitro and in vivo. PepA and two other peptides with shuffled sequences were assayed upon different binomials of host cell/parasite, including professional [as peritoneal mouse macrophages (PMM)] and non-professional phagocytes [primary cultures of cardiac cells (CM)], under different protocols. Also, their impact was further addressed in vivo using a mouse model of acute experimental Chagas disease. Our in-vitro findings demonstrate that PepA and PepB (the peptide with random sequence retaining the “RS” sequence) reduced the intracellular parasitism of the PMM but were inactive during the infection of cardiac cells. Another set of in-vitro and in-vivo studies showed that they do not display a trypanocidal effect on bloodstream trypomastigotes nor exhibit in-vivo efficacy when administered after the parasite inoculation. Our data report the in-vitro activity of PepA and PepB upon the infection of PMM by T. cruzi, possibly triggering the microbicidal arsenal of the host professional phagocytes, capable of controlling parasitic invasion and proliferation.
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spelling pubmed-91210622022-05-21 The Impact of the CTHRSSVVC Peptide Upon Experimental Models of Trypanosoma cruzi Infection Leite, Gabriela Rodrigues Batista, Denise da Gama Jaén Mazzeti, Ana Lia Silva, Rosemeire Aparecida Lugão, Ademar Benévolo Soeiro, Maria de Nazaré Correia Front Cell Infect Microbiol Cellular and Infection Microbiology Chagas disease (CD), caused by the hemoflagellate protozoan Trypanosoma cruzi, affects more than six million people worldwide and presents an unsatisfactory therapy, based on two nitroderivatives, introduced in clinical medicine for decades. The synthetic peptide, with CTHRSSVVC sequence (PepA), mimics the CD163 and TNF-α tripeptide “RSS” motif and binds to atheromatous plaques in carotid biopsies of human patients, spleen tissues, and a low-density lipoprotein receptor knockout (LDLr−/−) mouse model of atherosclerosis. CD163 receptor is present on monocytes, macrophages, and neutrophils, acting as a regulator of acute-phase processes and modulating aspects of the inflammatory response and the establishment of infections. Due to the potential theranostic role of PepA, our aim was to investigate its effect upon T. cruzi infection in vitro and in vivo. PepA and two other peptides with shuffled sequences were assayed upon different binomials of host cell/parasite, including professional [as peritoneal mouse macrophages (PMM)] and non-professional phagocytes [primary cultures of cardiac cells (CM)], under different protocols. Also, their impact was further addressed in vivo using a mouse model of acute experimental Chagas disease. Our in-vitro findings demonstrate that PepA and PepB (the peptide with random sequence retaining the “RS” sequence) reduced the intracellular parasitism of the PMM but were inactive during the infection of cardiac cells. Another set of in-vitro and in-vivo studies showed that they do not display a trypanocidal effect on bloodstream trypomastigotes nor exhibit in-vivo efficacy when administered after the parasite inoculation. Our data report the in-vitro activity of PepA and PepB upon the infection of PMM by T. cruzi, possibly triggering the microbicidal arsenal of the host professional phagocytes, capable of controlling parasitic invasion and proliferation. Frontiers Media S.A. 2022-05-06 /pmc/articles/PMC9121062/ /pubmed/35601101 http://dx.doi.org/10.3389/fcimb.2022.882555 Text en Copyright © 2022 Leite, Batista, Mazzeti, Silva, Lugão and Soeiro https://creativecommons.org/licenses/by/4.0/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(s) 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.
spellingShingle Cellular and Infection Microbiology
Leite, Gabriela Rodrigues
Batista, Denise da Gama Jaén
Mazzeti, Ana Lia
Silva, Rosemeire Aparecida
Lugão, Ademar Benévolo
Soeiro, Maria de Nazaré Correia
The Impact of the CTHRSSVVC Peptide Upon Experimental Models of Trypanosoma cruzi Infection
title The Impact of the CTHRSSVVC Peptide Upon Experimental Models of Trypanosoma cruzi Infection
title_full The Impact of the CTHRSSVVC Peptide Upon Experimental Models of Trypanosoma cruzi Infection
title_fullStr The Impact of the CTHRSSVVC Peptide Upon Experimental Models of Trypanosoma cruzi Infection
title_full_unstemmed The Impact of the CTHRSSVVC Peptide Upon Experimental Models of Trypanosoma cruzi Infection
title_short The Impact of the CTHRSSVVC Peptide Upon Experimental Models of Trypanosoma cruzi Infection
title_sort impact of the cthrssvvc peptide upon experimental models of trypanosoma cruzi infection
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121062/
https://www.ncbi.nlm.nih.gov/pubmed/35601101
http://dx.doi.org/10.3389/fcimb.2022.882555
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