RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis

Background Trypanosoma cruzi is a protozoan parasite responsible for Chagas disease, affecting millions globally. This parasite infects mammalian host cells, particularly macrophages. The interaction between T. cruzi and macrophages involves intricate signaling pathways mediated by pattern recogniti...

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Autores: Callejas-Hernández, Francisco, Herreros-Cabello, Alfonso, Poveda, Cristina, Maza, María C., Mares, José Francisco, Santos-Peñaloza, Diana K., Fresno Escudero, Manuel, Gironés Pujol, Nuria
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:dnet:biblosearchi::9b69d94f90efad9b277de87f4540fd3a
Acceso en línea:https://hdl.handle.net/10486/761340
https://dx.doi.org/10.1093/infdis/jiaf074
Access Level:acceso abierto
Palabra clave:Trypanosoma cruzi
Chagas disease
macrophages
Toll-like receptor
transferrin receptor
Biología y Biomedicina / Biología
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spelling RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix BiosynthesisCallejas-Hernández, FranciscoHerreros-Cabello, AlfonsoPoveda, CristinaMaza, María C.Mares, José FranciscoSantos-Peñaloza, Diana K.Fresno Escudero, ManuelGironés Pujol, NuriaTrypanosoma cruziChagas diseasemacrophagesToll-like receptortransferrin receptorBiología y Biomedicina / BiologíaBackground Trypanosoma cruzi is a protozoan parasite responsible for Chagas disease, affecting millions globally. This parasite infects mammalian host cells, particularly macrophages. The interaction between T. cruzi and macrophages involves intricate signaling pathways mediated by pattern recognition receptors, which lead to the production of immune mediators, that are parasite-strain dependent and not completely understood. Methods We conducted an unbiased transcriptomic analysis of the immune response in mouse macrophages 24 hours postinfection with the Y strain of T. cruzi using RNA-Seq and validated and compared the results using quantitative RT-PCR in macrophages infected with the Y and the VFRA T. cruzi strains. Results Bioinformatics analysis of the transcriptomics results evidenced a key role of Toll-like receptor 2 (Tlr2) and Tlr7 in the immune response against the parasite that was parasite-dependent. Tlr2 signaling was more activated with the VFRA strain and Tlr7 with the Y strain. Gene ontology analyses predicted a blockage in iron transport mediated by clathrin and the modulation of the extracellular matrix biosynthesis, which were validated by RT-qPCR. Infection with the VFRA strain provoked the inhibition of ferritin, which correlated with parasite proliferation. Conclusions Our study recapitulates knowledge on the response of macrophages and provides insights into the importance of TLR2 and TLR7, iron metabolism, and extracellular matrix in the infected macrophage, which help the understanding of molecular mechanisms underlying T. cruzi infection in macrophages with strains with different virulence. These findings are crucial for identifying novel therapeutic targets and advancing strategies to combat Chagas disease.This work was supported the Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (grant numbers PGC2018-096132-B-I00 and PID2021-123389OB-I00 to N. G.); Ministerio de Ciencia e Innovación (grant number PID2022-137487OB-I00 to M. F.); Comunidad de Madrid (grant number S2017/BMD-3671 INFLAMUNE-CM; FEDER to M. F.); Instituto de Salud Carlos III, Red de Investigación Cooperativa en Enfermedades Tropicales (grant number RD16/0027/0006 to M. F.); and institutional grants from Fundación Ramón Areces and Banco de SantanderOxford University PressDepartamento de Biología MolecularFacultad de CienciasGobierno de EspañaComunidad de Madrid20252025-06-15research articlehttp://purl.org/coar/resource_type/c_2df8fbb1EVoRhttp://purl.org/coar/version/c_dc82b40f9837b551info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10486/761340https://dx.doi.org/10.1093/infdis/jiaf07439948431reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:biblosearchi::9b69d94f90efad9b277de87f4540fd3a2026-06-23T12:46:27Z
dc.title.none.fl_str_mv RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis
title RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis
spellingShingle RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis
Callejas-Hernández, Francisco
Trypanosoma cruzi
Chagas disease
macrophages
Toll-like receptor
transferrin receptor
Biología y Biomedicina / Biología
title_short RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis
title_full RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis
title_fullStr RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis
title_full_unstemmed RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis
title_sort RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis
dc.creator.none.fl_str_mv Callejas-Hernández, Francisco
Herreros-Cabello, Alfonso
Poveda, Cristina
Maza, María C.
Mares, José Francisco
Santos-Peñaloza, Diana K.
Fresno Escudero, Manuel
Gironés Pujol, Nuria
author Callejas-Hernández, Francisco
author_facet Callejas-Hernández, Francisco
Herreros-Cabello, Alfonso
Poveda, Cristina
Maza, María C.
Mares, José Francisco
Santos-Peñaloza, Diana K.
Fresno Escudero, Manuel
Gironés Pujol, Nuria
author_role author
author2 Herreros-Cabello, Alfonso
Poveda, Cristina
Maza, María C.
Mares, José Francisco
Santos-Peñaloza, Diana K.
Fresno Escudero, Manuel
Gironés Pujol, Nuria
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
Gobierno de España
Comunidad de Madrid
dc.subject.none.fl_str_mv Trypanosoma cruzi
Chagas disease
macrophages
Toll-like receptor
transferrin receptor
Biología y Biomedicina / Biología
topic Trypanosoma cruzi
Chagas disease
macrophages
Toll-like receptor
transferrin receptor
Biología y Biomedicina / Biología
description Background Trypanosoma cruzi is a protozoan parasite responsible for Chagas disease, affecting millions globally. This parasite infects mammalian host cells, particularly macrophages. The interaction between T. cruzi and macrophages involves intricate signaling pathways mediated by pattern recognition receptors, which lead to the production of immune mediators, that are parasite-strain dependent and not completely understood. Methods We conducted an unbiased transcriptomic analysis of the immune response in mouse macrophages 24 hours postinfection with the Y strain of T. cruzi using RNA-Seq and validated and compared the results using quantitative RT-PCR in macrophages infected with the Y and the VFRA T. cruzi strains. Results Bioinformatics analysis of the transcriptomics results evidenced a key role of Toll-like receptor 2 (Tlr2) and Tlr7 in the immune response against the parasite that was parasite-dependent. Tlr2 signaling was more activated with the VFRA strain and Tlr7 with the Y strain. Gene ontology analyses predicted a blockage in iron transport mediated by clathrin and the modulation of the extracellular matrix biosynthesis, which were validated by RT-qPCR. Infection with the VFRA strain provoked the inhibition of ferritin, which correlated with parasite proliferation. Conclusions Our study recapitulates knowledge on the response of macrophages and provides insights into the importance of TLR2 and TLR7, iron metabolism, and extracellular matrix in the infected macrophage, which help the understanding of molecular mechanisms underlying T. cruzi infection in macrophages with strains with different virulence. These findings are crucial for identifying novel therapeutic targets and advancing strategies to combat Chagas disease.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-06-15
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
EVoR
http://purl.org/coar/version/c_dc82b40f9837b551
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10486/761340
https://dx.doi.org/10.1093/infdis/jiaf074
39948431
url https://hdl.handle.net/10486/761340
https://dx.doi.org/10.1093/infdis/jiaf074
identifier_str_mv 39948431
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
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repository.mail.fl_str_mv
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