Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells

Autores
Santamaria, Miguel H.; Perez Caballero, Eugenia; Corral, Ricardo Santiago
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The gut epithelial barrier is a strategic place to prevent, or at least to limit, parasite dissemination upon oral infection with Toxoplasma gondii. Innate immunity to this pathogen results from delicate interactions involving different components of the infecting agent and the host. We herein aimed to examine the molecular mechanism by which protozoan DNA boosts the production of α-defensin-5 (DEFA-5), the main antimicrobial peptide at the target site of infection. The present study shows that DEFA-5 is rapidly upregulated in intestinal epithelial cells following intracellular Toll-like receptor 9 (TLR9) activation by unmethylated CpG motifs in DNA from T. gondii (CpG-DNA). Concomitantly, CpG-DNA purified from the pathogen markedly increased TLR9 mRNA expression levels in the Caco-2 cell line. We further verified that DEFA-5 production was dependent on interferon-β released from these cells upon treatment with CpG-DNA prepared from tachyzoites. Our results suggest that, in protozoan DNA-stimulated intestinal epithelial cells, the TLR9/interferon-β/DEFA-5 pathway may initiate an innate anti-T. gondii response without the need of parasite invasion. These findings highlight the key role of the gut epithelium in Toxoplasma recognition and amplification of local host defence against this microbe, thereby contributing to gain insight into immunoprotective mechanisms and to improve therapeutic strategies.
Fil: Santamaria, Miguel H.. Centro de Estudios Metabólicos; España
Fil: Perez Caballero, Eugenia. Centro de Estudios Metabólicos; España
Fil: Corral, Ricardo Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Toxoplasma Gondii
Alpha Defensin
Cpg Dna
Toll-Like Receptor 9
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/42490
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/42490
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cellsSantamaria, Miguel H.Perez Caballero, EugeniaCorral, Ricardo SantiagoToxoplasma GondiiAlpha DefensinCpg DnaToll-Like Receptor 9https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The gut epithelial barrier is a strategic place to prevent, or at least to limit, parasite dissemination upon oral infection with Toxoplasma gondii. Innate immunity to this pathogen results from delicate interactions involving different components of the infecting agent and the host. We herein aimed to examine the molecular mechanism by which protozoan DNA boosts the production of α-defensin-5 (DEFA-5), the main antimicrobial peptide at the target site of infection. The present study shows that DEFA-5 is rapidly upregulated in intestinal epithelial cells following intracellular Toll-like receptor 9 (TLR9) activation by unmethylated CpG motifs in DNA from T. gondii (CpG-DNA). Concomitantly, CpG-DNA purified from the pathogen markedly increased TLR9 mRNA expression levels in the Caco-2 cell line. We further verified that DEFA-5 production was dependent on interferon-β released from these cells upon treatment with CpG-DNA prepared from tachyzoites. Our results suggest that, in protozoan DNA-stimulated intestinal epithelial cells, the TLR9/interferon-β/DEFA-5 pathway may initiate an innate anti-T. gondii response without the need of parasite invasion. These findings highlight the key role of the gut epithelium in Toxoplasma recognition and amplification of local host defence against this microbe, thereby contributing to gain insight into immunoprotective mechanisms and to improve therapeutic strategies.Fil: Santamaria, Miguel H.. Centro de Estudios Metabólicos; EspañaFil: Perez Caballero, Eugenia. Centro de Estudios Metabólicos; EspañaFil: Corral, Ricardo Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaCambridge University Press2015-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/42490Santamaria, Miguel H.; Perez Caballero, Eugenia; Corral, Ricardo Santiago; Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells; Cambridge University Press; Parasitology; 143; 1; 11-2015; 60-680031-1820CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1017/S0031182015001456info:eu-repo/semantics/altIdentifier/url/https://www.cambridge.org/core/journals/parasitology/article/unmethylated-cpg-motifs-in-toxoplasma-gondii-dna-induce-tlr9-and-ifndependent-expression-of-defensin5-in-intestinal-epithelial-cells/D0F9A3FDEBE962D8C9480440501AC7FAinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:17Zoai:ri.conicet.gov.ar:11336/42490instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:59:17.331CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells
title Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells
spellingShingle Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells
Santamaria, Miguel H.
Toxoplasma Gondii
Alpha Defensin
Cpg Dna
Toll-Like Receptor 9
title_short Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells
title_full Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells
title_fullStr Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells
title_full_unstemmed Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells
title_sort Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells
dc.creator.none.fl_str_mv Santamaria, Miguel H.
Perez Caballero, Eugenia
Corral, Ricardo Santiago
author Santamaria, Miguel H.
author_facet Santamaria, Miguel H.
Perez Caballero, Eugenia
Corral, Ricardo Santiago
author_role author
author2 Perez Caballero, Eugenia
Corral, Ricardo Santiago
author2_role author
author
dc.subject.none.fl_str_mv Toxoplasma Gondii
Alpha Defensin
Cpg Dna
Toll-Like Receptor 9
topic Toxoplasma Gondii
Alpha Defensin
Cpg Dna
Toll-Like Receptor 9
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The gut epithelial barrier is a strategic place to prevent, or at least to limit, parasite dissemination upon oral infection with Toxoplasma gondii. Innate immunity to this pathogen results from delicate interactions involving different components of the infecting agent and the host. We herein aimed to examine the molecular mechanism by which protozoan DNA boosts the production of α-defensin-5 (DEFA-5), the main antimicrobial peptide at the target site of infection. The present study shows that DEFA-5 is rapidly upregulated in intestinal epithelial cells following intracellular Toll-like receptor 9 (TLR9) activation by unmethylated CpG motifs in DNA from T. gondii (CpG-DNA). Concomitantly, CpG-DNA purified from the pathogen markedly increased TLR9 mRNA expression levels in the Caco-2 cell line. We further verified that DEFA-5 production was dependent on interferon-β released from these cells upon treatment with CpG-DNA prepared from tachyzoites. Our results suggest that, in protozoan DNA-stimulated intestinal epithelial cells, the TLR9/interferon-β/DEFA-5 pathway may initiate an innate anti-T. gondii response without the need of parasite invasion. These findings highlight the key role of the gut epithelium in Toxoplasma recognition and amplification of local host defence against this microbe, thereby contributing to gain insight into immunoprotective mechanisms and to improve therapeutic strategies.
Fil: Santamaria, Miguel H.. Centro de Estudios Metabólicos; España
Fil: Perez Caballero, Eugenia. Centro de Estudios Metabólicos; España
Fil: Corral, Ricardo Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The gut epithelial barrier is a strategic place to prevent, or at least to limit, parasite dissemination upon oral infection with Toxoplasma gondii. Innate immunity to this pathogen results from delicate interactions involving different components of the infecting agent and the host. We herein aimed to examine the molecular mechanism by which protozoan DNA boosts the production of α-defensin-5 (DEFA-5), the main antimicrobial peptide at the target site of infection. The present study shows that DEFA-5 is rapidly upregulated in intestinal epithelial cells following intracellular Toll-like receptor 9 (TLR9) activation by unmethylated CpG motifs in DNA from T. gondii (CpG-DNA). Concomitantly, CpG-DNA purified from the pathogen markedly increased TLR9 mRNA expression levels in the Caco-2 cell line. We further verified that DEFA-5 production was dependent on interferon-β released from these cells upon treatment with CpG-DNA prepared from tachyzoites. Our results suggest that, in protozoan DNA-stimulated intestinal epithelial cells, the TLR9/interferon-β/DEFA-5 pathway may initiate an innate anti-T. gondii response without the need of parasite invasion. These findings highlight the key role of the gut epithelium in Toxoplasma recognition and amplification of local host defence against this microbe, thereby contributing to gain insight into immunoprotective mechanisms and to improve therapeutic strategies.
publishDate 2015
dc.date.none.fl_str_mv 2015-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/42490
Santamaria, Miguel H.; Perez Caballero, Eugenia; Corral, Ricardo Santiago; Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells; Cambridge University Press; Parasitology; 143; 1; 11-2015; 60-68
0031-1820
CONICET Digital
CONICET
url http://hdl.handle.net/11336/42490
identifier_str_mv Santamaria, Miguel H.; Perez Caballero, Eugenia; Corral, Ricardo Santiago; Unmethylated CpG motifs in Toxoplasma gondii DNA induce TLR9- and IFN-β-dependent expression of α-defensin-5 in intestinal epithelial cells; Cambridge University Press; Parasitology; 143; 1; 11-2015; 60-68
0031-1820
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1017/S0031182015001456
info:eu-repo/semantics/altIdentifier/url/https://www.cambridge.org/core/journals/parasitology/article/unmethylated-cpg-motifs-in-toxoplasma-gondii-dna-induce-tlr9-and-ifndependent-expression-of-defensin5-in-intestinal-epithelial-cells/D0F9A3FDEBE962D8C9480440501AC7FA
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cambridge University Press
publisher.none.fl_str_mv Cambridge University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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