Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.

Tc24-C4, a modified recombinant flagellar calcium-binding protein of Trypanosoma cruzi, is under development as a therapeutic subunit vaccine candidate to prevent or delay progression of chronic Chagasic cardiomyopathy. When combined with Toll-like receptor agonists, Tc24-C4 immunization reduces par...

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Autores principales:	Leroy Versteeg, Rakesh Adhikari, Cristina Poveda, Maria Jose Villar-Mondragon, Kathryn M Jones, Peter J Hotez, Maria Elena Bottazzi, Edwin Tijhaar, Jeroen Pollet
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/58d767582fa0422791889d37f049cef3
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spelling	oai:doaj.org-article:58d767582fa0422791889d37f049cef32021-12-02T20:24:11ZLocation and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.1935-27271935-273510.1371/journal.pntd.0009689https://doaj.org/article/58d767582fa0422791889d37f049cef32021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009689https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Tc24-C4, a modified recombinant flagellar calcium-binding protein of Trypanosoma cruzi, is under development as a therapeutic subunit vaccine candidate to prevent or delay progression of chronic Chagasic cardiomyopathy. When combined with Toll-like receptor agonists, Tc24-C4 immunization reduces parasitemia, parasites in cardiac tissue, and cardiac fibrosis and inflammation in animal models. To support further research on the vaccine candidate and its mechanism of action, murine monoclonal antibodies (mAbs) against Tc24-C4 were generated. Here, we report new findings made with mAb Tc24-C4/884 that detects Tc24-WT and Tc24-C4, as well as native Tc24 in T. cruzi on ELISA, western blots, and different imaging techniques. Surprisingly, detection of Tc24 by Tc24-C/884 in fixed T. cruzi trypomastigotes required permeabilization of the parasite, revealing that Tc24 is not exposed on the surface of T. cruzi, making a direct role of antibodies in the induced protection after Tc24-C4 immunization less likely. We further observed that after immunostaining T. cruzi-infected cells with mAb Tc24-C4/884, the expression of Tc24 decreases significantly when T. cruzi trypomastigotes enter host cells and transform into amastigotes. However, Tc24 is then upregulated in association with parasite flagellar growth linked to re-transformation into the trypomastigote form, prior to host cellular escape. These observations are discussed in the context of potential mechanisms of vaccine immunity.Leroy VersteegRakesh AdhikariCristina PovedaMaria Jose Villar-MondragonKathryn M JonesPeter J HotezMaria Elena BottazziEdwin TijhaarJeroen PolletPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009689 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Leroy Versteeg Rakesh Adhikari Cristina Poveda Maria Jose Villar-Mondragon Kathryn M Jones Peter J Hotez Maria Elena Bottazzi Edwin Tijhaar Jeroen Pollet Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.
description	Tc24-C4, a modified recombinant flagellar calcium-binding protein of Trypanosoma cruzi, is under development as a therapeutic subunit vaccine candidate to prevent or delay progression of chronic Chagasic cardiomyopathy. When combined with Toll-like receptor agonists, Tc24-C4 immunization reduces parasitemia, parasites in cardiac tissue, and cardiac fibrosis and inflammation in animal models. To support further research on the vaccine candidate and its mechanism of action, murine monoclonal antibodies (mAbs) against Tc24-C4 were generated. Here, we report new findings made with mAb Tc24-C4/884 that detects Tc24-WT and Tc24-C4, as well as native Tc24 in T. cruzi on ELISA, western blots, and different imaging techniques. Surprisingly, detection of Tc24 by Tc24-C/884 in fixed T. cruzi trypomastigotes required permeabilization of the parasite, revealing that Tc24 is not exposed on the surface of T. cruzi, making a direct role of antibodies in the induced protection after Tc24-C4 immunization less likely. We further observed that after immunostaining T. cruzi-infected cells with mAb Tc24-C4/884, the expression of Tc24 decreases significantly when T. cruzi trypomastigotes enter host cells and transform into amastigotes. However, Tc24 is then upregulated in association with parasite flagellar growth linked to re-transformation into the trypomastigote form, prior to host cellular escape. These observations are discussed in the context of potential mechanisms of vaccine immunity.
format	article
author	Leroy Versteeg Rakesh Adhikari Cristina Poveda Maria Jose Villar-Mondragon Kathryn M Jones Peter J Hotez Maria Elena Bottazzi Edwin Tijhaar Jeroen Pollet
author_facet	Leroy Versteeg Rakesh Adhikari Cristina Poveda Maria Jose Villar-Mondragon Kathryn M Jones Peter J Hotez Maria Elena Bottazzi Edwin Tijhaar Jeroen Pollet
author_sort	Leroy Versteeg
title	Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.
title_short	Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.
title_full	Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.
title_fullStr	Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.
title_full_unstemmed	Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.
title_sort	location and expression kinetics of tc24 in different life stages of trypanosoma cruzi.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/58d767582fa0422791889d37f049cef3
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Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.

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