Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro

Autores
Natale, Maria Ailen; Minning, Todd; Albareda, María Cecilia; Castro Eiro, Melisa Daiana; Álvarez, María Gabriela; Lococo, Bruno Edgardo; Cesar, Gonzalo Leandro; Bertocchi, Graciela Luciana; Elias, Maria Josefina; Caputo, María Belén; Tarleton, Rick Lee; Laucella, Susana Adriana
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In chronic Chagas disease, Trypanosoma cruzi-specific T-cell function decreases over time, and alterations in the homeostatic IL-7/IL-7R axis are evident, consistent with a process of immune exhaustion. IL-27 is an important immunoregulatory cytokine that shares Tcell signaling with IL-7 and other cytokines of the IL-12 family and might be involved in the transcriptional regulation of T-cell function. Here, we evaluated the expression and function of IL-27R in antigen-experienced T cells from subjects with chronic Chagas disease and assessed whether in vitro treatment with IL-27 and IL-7 might improve T. cruzi-specific polyfunctional T-cell responses. In vitro exposure of PBMCs to T. cruzi induced a downregulation of IL-27R in CD4+ T cells and an upregulation in CD8+ T cells in subjects without heart disease, while IL-27R expression remained unaltered in subjects with more severe clinical stages. The modulation of IL-27R was associated with functional signaling through STAT3 and STAT5 and induction of the downstream genes TBX21, EOMES and CXCL9 in response to IL-27. In vitro treatment of PBMCs with IL-27 and IL-7 improved monofunctional and polyfunctional Th1 responses, accompanied by the induction of IL-10 and Bcl-2 expression in subjects without heart disease but did not improve those in subjects with cardiomyopathy. Our findings support the process of desensitization of the IL-27/IL-27R pathway along with disease severity and that the pro-inflammatory and immunomodulatory mechanisms of IL-27 might be interconnected.
Fil: Natale, Maria Ailen. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Minning, Todd. University of Georgia; Estados Unidos
Fil: Albareda, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Castro Eiro, Melisa Daiana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Álvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina
Fil: Lococo, Bruno Edgardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina
Fil: Cesar, Gonzalo Leandro. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bertocchi, Graciela Luciana. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina
Fil: Elias, Maria Josefina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Caputo, María Belén. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Tarleton, Rick Lee. University of Georgia; Estados Unidos
Fil: Laucella, Susana Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina
Materia
LINFOCITOS T
T CRUZI
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:11336/165645
Acceder
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spelling Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitroNatale, Maria AilenMinning, ToddAlbareda, María CeciliaCastro Eiro, Melisa DaianaÁlvarez, María GabrielaLococo, Bruno EdgardoCesar, Gonzalo LeandroBertocchi, Graciela LucianaElias, Maria JosefinaCaputo, María BelénTarleton, Rick LeeLaucella, Susana AdrianaLINFOCITOS TT CRUZIhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3In chronic Chagas disease, Trypanosoma cruzi-specific T-cell function decreases over time, and alterations in the homeostatic IL-7/IL-7R axis are evident, consistent with a process of immune exhaustion. IL-27 is an important immunoregulatory cytokine that shares Tcell signaling with IL-7 and other cytokines of the IL-12 family and might be involved in the transcriptional regulation of T-cell function. Here, we evaluated the expression and function of IL-27R in antigen-experienced T cells from subjects with chronic Chagas disease and assessed whether in vitro treatment with IL-27 and IL-7 might improve T. cruzi-specific polyfunctional T-cell responses. In vitro exposure of PBMCs to T. cruzi induced a downregulation of IL-27R in CD4+ T cells and an upregulation in CD8+ T cells in subjects without heart disease, while IL-27R expression remained unaltered in subjects with more severe clinical stages. The modulation of IL-27R was associated with functional signaling through STAT3 and STAT5 and induction of the downstream genes TBX21, EOMES and CXCL9 in response to IL-27. In vitro treatment of PBMCs with IL-27 and IL-7 improved monofunctional and polyfunctional Th1 responses, accompanied by the induction of IL-10 and Bcl-2 expression in subjects without heart disease but did not improve those in subjects with cardiomyopathy. Our findings support the process of desensitization of the IL-27/IL-27R pathway along with disease severity and that the pro-inflammatory and immunomodulatory mechanisms of IL-27 might be interconnected.Fil: Natale, Maria Ailen. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Minning, Todd. University of Georgia; Estados UnidosFil: Albareda, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Castro Eiro, Melisa Daiana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Álvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Lococo, Bruno Edgardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Cesar, Gonzalo Leandro. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bertocchi, Graciela Luciana. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Elias, Maria Josefina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Caputo, María Belén. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Tarleton, Rick Lee. University of Georgia; Estados UnidosFil: Laucella, Susana Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaPublic Library of Science2021-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/165645Natale, Maria Ailen; Minning, Todd; Albareda, María Cecilia; Castro Eiro, Melisa Daiana; Álvarez, María Gabriela; et al.; Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro; Public Library of Science; PLoS Neglected Tropical Diseases; 15; 6; 6-2021; 1-241935-27271935-2735CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0009473info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:41Zoai:ri.conicet.gov.ar:11336/165645instacron: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:34982025-09-29 09:44:41.397CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro
title Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro
spellingShingle Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro
Natale, Maria Ailen
LINFOCITOS T
T CRUZI
title_short Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro
title_full Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro
title_fullStr Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro
title_full_unstemmed Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro
title_sort Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro
dc.creator.none.fl_str_mv Natale, Maria Ailen
Minning, Todd
Albareda, María Cecilia
Castro Eiro, Melisa Daiana
Álvarez, María Gabriela
Lococo, Bruno Edgardo
Cesar, Gonzalo Leandro
Bertocchi, Graciela Luciana
Elias, Maria Josefina
Caputo, María Belén
Tarleton, Rick Lee
Laucella, Susana Adriana
author Natale, Maria Ailen
author_facet Natale, Maria Ailen
Minning, Todd
Albareda, María Cecilia
Castro Eiro, Melisa Daiana
Álvarez, María Gabriela
Lococo, Bruno Edgardo
Cesar, Gonzalo Leandro
Bertocchi, Graciela Luciana
Elias, Maria Josefina
Caputo, María Belén
Tarleton, Rick Lee
Laucella, Susana Adriana
author_role author
author2 Minning, Todd
Albareda, María Cecilia
Castro Eiro, Melisa Daiana
Álvarez, María Gabriela
Lococo, Bruno Edgardo
Cesar, Gonzalo Leandro
Bertocchi, Graciela Luciana
Elias, Maria Josefina
Caputo, María Belén
Tarleton, Rick Lee
Laucella, Susana Adriana
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv LINFOCITOS T
T CRUZI
topic LINFOCITOS T
T CRUZI
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In chronic Chagas disease, Trypanosoma cruzi-specific T-cell function decreases over time, and alterations in the homeostatic IL-7/IL-7R axis are evident, consistent with a process of immune exhaustion. IL-27 is an important immunoregulatory cytokine that shares Tcell signaling with IL-7 and other cytokines of the IL-12 family and might be involved in the transcriptional regulation of T-cell function. Here, we evaluated the expression and function of IL-27R in antigen-experienced T cells from subjects with chronic Chagas disease and assessed whether in vitro treatment with IL-27 and IL-7 might improve T. cruzi-specific polyfunctional T-cell responses. In vitro exposure of PBMCs to T. cruzi induced a downregulation of IL-27R in CD4+ T cells and an upregulation in CD8+ T cells in subjects without heart disease, while IL-27R expression remained unaltered in subjects with more severe clinical stages. The modulation of IL-27R was associated with functional signaling through STAT3 and STAT5 and induction of the downstream genes TBX21, EOMES and CXCL9 in response to IL-27. In vitro treatment of PBMCs with IL-27 and IL-7 improved monofunctional and polyfunctional Th1 responses, accompanied by the induction of IL-10 and Bcl-2 expression in subjects without heart disease but did not improve those in subjects with cardiomyopathy. Our findings support the process of desensitization of the IL-27/IL-27R pathway along with disease severity and that the pro-inflammatory and immunomodulatory mechanisms of IL-27 might be interconnected.
Fil: Natale, Maria Ailen. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Minning, Todd. University of Georgia; Estados Unidos
Fil: Albareda, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Castro Eiro, Melisa Daiana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Álvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina
Fil: Lococo, Bruno Edgardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina
Fil: Cesar, Gonzalo Leandro. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bertocchi, Graciela Luciana. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina
Fil: Elias, Maria Josefina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Caputo, María Belén. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Tarleton, Rick Lee. University of Georgia; Estados Unidos
Fil: Laucella, Susana Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina
description In chronic Chagas disease, Trypanosoma cruzi-specific T-cell function decreases over time, and alterations in the homeostatic IL-7/IL-7R axis are evident, consistent with a process of immune exhaustion. IL-27 is an important immunoregulatory cytokine that shares Tcell signaling with IL-7 and other cytokines of the IL-12 family and might be involved in the transcriptional regulation of T-cell function. Here, we evaluated the expression and function of IL-27R in antigen-experienced T cells from subjects with chronic Chagas disease and assessed whether in vitro treatment with IL-27 and IL-7 might improve T. cruzi-specific polyfunctional T-cell responses. In vitro exposure of PBMCs to T. cruzi induced a downregulation of IL-27R in CD4+ T cells and an upregulation in CD8+ T cells in subjects without heart disease, while IL-27R expression remained unaltered in subjects with more severe clinical stages. The modulation of IL-27R was associated with functional signaling through STAT3 and STAT5 and induction of the downstream genes TBX21, EOMES and CXCL9 in response to IL-27. In vitro treatment of PBMCs with IL-27 and IL-7 improved monofunctional and polyfunctional Th1 responses, accompanied by the induction of IL-10 and Bcl-2 expression in subjects without heart disease but did not improve those in subjects with cardiomyopathy. Our findings support the process of desensitization of the IL-27/IL-27R pathway along with disease severity and that the pro-inflammatory and immunomodulatory mechanisms of IL-27 might be interconnected.
publishDate 2021
dc.date.none.fl_str_mv 2021-06
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/11336/165645
Natale, Maria Ailen; Minning, Todd; Albareda, María Cecilia; Castro Eiro, Melisa Daiana; Álvarez, María Gabriela; et al.; Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro; Public Library of Science; PLoS Neglected Tropical Diseases; 15; 6; 6-2021; 1-24
1935-2727
1935-2735
CONICET Digital
CONICET
url http://hdl.handle.net/11336/165645
identifier_str_mv Natale, Maria Ailen; Minning, Todd; Albareda, María Cecilia; Castro Eiro, Melisa Daiana; Álvarez, María Gabriela; et al.; Immune exhaustion in chronic chagas disease: Pro-inflammatory and immunomodulatory action of il-27 in vitro; Public Library of Science; PLoS Neglected Tropical Diseases; 15; 6; 6-2021; 1-24
1935-2727
1935-2735
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0009473
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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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 Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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