Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection

Autores
Costa, Monique; da Costa, Valeria; Frigerio, Sofía; Festari, María Florencia; Landeira, Mercedes; Rodríguez Zraquia, Santiago A.; Lores, Pablo; Carasi, Paula; Freire Gard, Teresa Inés
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fasciola hepatica is a fluke that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. The parasite regulates the host immune system by inducing a strong Th2 and regulatory T (Treg) cell immune response through mechanisms that might involve the expression or activity of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that also has immunoregulatory and antioxidant properties. In this paper, we show that F. hepatica-infected mice upregulate HO-1 on peritoneal antigen-presenting cells (APC), which produce decreased levels of both reactive oxygen and nitrogen species (ROS/RNS). The presence of these cells was associated with increased levels of regulatory T cells (Tregs). Blocking the IL-10 receptor (IL-10R) during parasite infection demonstrated that the presence of splenic Tregs and peritoneal APC expressing HO-1 were both dependent on IL-10 activity. Furthermore, IL-10R neutralization as well as pharmacological treatment with the HO-1 inhibitor SnPP protected mice from parasite infection and allowed peritoneal APC to produce significantly higher ROS/RNS levels than those detected in cells from infected control mice. Finally, parasite infection carried out in gp91phox knockout mice with inactive NADPH oxidase was associated with decreased levels of peritoneal HO-1+ cells and splenic Tregs, and partially protected mice from the hepatic damage induced by the parasite, revealing the complexity of the molecular mechanisms involving ROS production that participate in the complex pathology induced by this helminth. Altogether, these results contribute to the elucidation of the immunoregulatory and antioxidant role of HO-1 induced by F. hepatica in the host, providing alternative checkpoints that might control fasciolosis.
Fil: Costa, Monique. Universidad de la República; Uruguay
Fil: da Costa, Valeria. Universidad de la República; Uruguay
Fil: Frigerio, Sofía. Universidad de la República; Uruguay
Fil: Festari, María Florencia. Universidad de la República; Uruguay
Fil: Landeira, Mercedes. Universidad de la República; Uruguay
Fil: Rodríguez Zraquia, Santiago A.. Universidad de la República; Uruguay
Fil: Lores, Pablo. Universidad de la República; Uruguay
Fil: Carasi, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Freire Gard, Teresa Inés. Universidad de la República; Uruguay
Materia
ANTIGEN PRESENTING CELL
HELMINTH
HEME-OXIGENASE-1
IMMUNOREGULATION
REGULATORY T CELL
ROS/RNS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/179056
Acceder
id CONICETDig_121b3d252341c184545c14f30ef31c9a
oai_identifier_str oai:ri.conicet.gov.ar:11336/179056
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infectionCosta, Moniqueda Costa, ValeriaFrigerio, SofíaFestari, María FlorenciaLandeira, MercedesRodríguez Zraquia, Santiago A.Lores, PabloCarasi, PaulaFreire Gard, Teresa InésANTIGEN PRESENTING CELLHELMINTHHEME-OXIGENASE-1IMMUNOREGULATIONREGULATORY T CELLROS/RNShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Fasciola hepatica is a fluke that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. The parasite regulates the host immune system by inducing a strong Th2 and regulatory T (Treg) cell immune response through mechanisms that might involve the expression or activity of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that also has immunoregulatory and antioxidant properties. In this paper, we show that F. hepatica-infected mice upregulate HO-1 on peritoneal antigen-presenting cells (APC), which produce decreased levels of both reactive oxygen and nitrogen species (ROS/RNS). The presence of these cells was associated with increased levels of regulatory T cells (Tregs). Blocking the IL-10 receptor (IL-10R) during parasite infection demonstrated that the presence of splenic Tregs and peritoneal APC expressing HO-1 were both dependent on IL-10 activity. Furthermore, IL-10R neutralization as well as pharmacological treatment with the HO-1 inhibitor SnPP protected mice from parasite infection and allowed peritoneal APC to produce significantly higher ROS/RNS levels than those detected in cells from infected control mice. Finally, parasite infection carried out in gp91phox knockout mice with inactive NADPH oxidase was associated with decreased levels of peritoneal HO-1+ cells and splenic Tregs, and partially protected mice from the hepatic damage induced by the parasite, revealing the complexity of the molecular mechanisms involving ROS production that participate in the complex pathology induced by this helminth. Altogether, these results contribute to the elucidation of the immunoregulatory and antioxidant role of HO-1 induced by F. hepatica in the host, providing alternative checkpoints that might control fasciolosis.Fil: Costa, Monique. Universidad de la República; UruguayFil: da Costa, Valeria. Universidad de la República; UruguayFil: Frigerio, Sofía. Universidad de la República; UruguayFil: Festari, María Florencia. Universidad de la República; UruguayFil: Landeira, Mercedes. Universidad de la República; UruguayFil: Rodríguez Zraquia, Santiago A.. Universidad de la República; UruguayFil: Lores, Pablo. Universidad de la República; UruguayFil: Carasi, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Freire Gard, Teresa Inés. Universidad de la República; UruguayMultidisciplinary Digital Publishing Institute2021-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/179056Costa, Monique; da Costa, Valeria; Frigerio, Sofía; Festari, María Florencia; Landeira, Mercedes; et al.; Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection; Multidisciplinary Digital Publishing Institute; Antioxidants; 10; 12; 12-2021; 1-212076-3921CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2076-3921/10/12/1938info:eu-repo/semantics/altIdentifier/doi/10.3390/antiox10121938info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:10:59Zoai:ri.conicet.gov.ar:11336/179056instacron: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:34982025-10-15 15:10:59.858CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection
title Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection
spellingShingle Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection
Costa, Monique
ANTIGEN PRESENTING CELL
HELMINTH
HEME-OXIGENASE-1
IMMUNOREGULATION
REGULATORY T CELL
ROS/RNS
title_short Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection
title_full Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection
title_fullStr Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection
title_full_unstemmed Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection
title_sort Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection
dc.creator.none.fl_str_mv Costa, Monique
da Costa, Valeria
Frigerio, Sofía
Festari, María Florencia
Landeira, Mercedes
Rodríguez Zraquia, Santiago A.
Lores, Pablo
Carasi, Paula
Freire Gard, Teresa Inés
author Costa, Monique
author_facet Costa, Monique
da Costa, Valeria
Frigerio, Sofía
Festari, María Florencia
Landeira, Mercedes
Rodríguez Zraquia, Santiago A.
Lores, Pablo
Carasi, Paula
Freire Gard, Teresa Inés
author_role author
author2 da Costa, Valeria
Frigerio, Sofía
Festari, María Florencia
Landeira, Mercedes
Rodríguez Zraquia, Santiago A.
Lores, Pablo
Carasi, Paula
Freire Gard, Teresa Inés
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTIGEN PRESENTING CELL
HELMINTH
HEME-OXIGENASE-1
IMMUNOREGULATION
REGULATORY T CELL
ROS/RNS
topic ANTIGEN PRESENTING CELL
HELMINTH
HEME-OXIGENASE-1
IMMUNOREGULATION
REGULATORY T CELL
ROS/RNS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Fasciola hepatica is a fluke that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. The parasite regulates the host immune system by inducing a strong Th2 and regulatory T (Treg) cell immune response through mechanisms that might involve the expression or activity of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that also has immunoregulatory and antioxidant properties. In this paper, we show that F. hepatica-infected mice upregulate HO-1 on peritoneal antigen-presenting cells (APC), which produce decreased levels of both reactive oxygen and nitrogen species (ROS/RNS). The presence of these cells was associated with increased levels of regulatory T cells (Tregs). Blocking the IL-10 receptor (IL-10R) during parasite infection demonstrated that the presence of splenic Tregs and peritoneal APC expressing HO-1 were both dependent on IL-10 activity. Furthermore, IL-10R neutralization as well as pharmacological treatment with the HO-1 inhibitor SnPP protected mice from parasite infection and allowed peritoneal APC to produce significantly higher ROS/RNS levels than those detected in cells from infected control mice. Finally, parasite infection carried out in gp91phox knockout mice with inactive NADPH oxidase was associated with decreased levels of peritoneal HO-1+ cells and splenic Tregs, and partially protected mice from the hepatic damage induced by the parasite, revealing the complexity of the molecular mechanisms involving ROS production that participate in the complex pathology induced by this helminth. Altogether, these results contribute to the elucidation of the immunoregulatory and antioxidant role of HO-1 induced by F. hepatica in the host, providing alternative checkpoints that might control fasciolosis.
Fil: Costa, Monique. Universidad de la República; Uruguay
Fil: da Costa, Valeria. Universidad de la República; Uruguay
Fil: Frigerio, Sofía. Universidad de la República; Uruguay
Fil: Festari, María Florencia. Universidad de la República; Uruguay
Fil: Landeira, Mercedes. Universidad de la República; Uruguay
Fil: Rodríguez Zraquia, Santiago A.. Universidad de la República; Uruguay
Fil: Lores, Pablo. Universidad de la República; Uruguay
Fil: Carasi, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Freire Gard, Teresa Inés. Universidad de la República; Uruguay
description Fasciola hepatica is a fluke that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. The parasite regulates the host immune system by inducing a strong Th2 and regulatory T (Treg) cell immune response through mechanisms that might involve the expression or activity of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that also has immunoregulatory and antioxidant properties. In this paper, we show that F. hepatica-infected mice upregulate HO-1 on peritoneal antigen-presenting cells (APC), which produce decreased levels of both reactive oxygen and nitrogen species (ROS/RNS). The presence of these cells was associated with increased levels of regulatory T cells (Tregs). Blocking the IL-10 receptor (IL-10R) during parasite infection demonstrated that the presence of splenic Tregs and peritoneal APC expressing HO-1 were both dependent on IL-10 activity. Furthermore, IL-10R neutralization as well as pharmacological treatment with the HO-1 inhibitor SnPP protected mice from parasite infection and allowed peritoneal APC to produce significantly higher ROS/RNS levels than those detected in cells from infected control mice. Finally, parasite infection carried out in gp91phox knockout mice with inactive NADPH oxidase was associated with decreased levels of peritoneal HO-1+ cells and splenic Tregs, and partially protected mice from the hepatic damage induced by the parasite, revealing the complexity of the molecular mechanisms involving ROS production that participate in the complex pathology induced by this helminth. Altogether, these results contribute to the elucidation of the immunoregulatory and antioxidant role of HO-1 induced by F. hepatica in the host, providing alternative checkpoints that might control fasciolosis.
publishDate 2021
dc.date.none.fl_str_mv 2021-12
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/11336/179056
Costa, Monique; da Costa, Valeria; Frigerio, Sofía; Festari, María Florencia; Landeira, Mercedes; et al.; Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection; Multidisciplinary Digital Publishing Institute; Antioxidants; 10; 12; 12-2021; 1-21
2076-3921
CONICET Digital
CONICET
url http://hdl.handle.net/11336/179056
identifier_str_mv Costa, Monique; da Costa, Valeria; Frigerio, Sofía; Festari, María Florencia; Landeira, Mercedes; et al.; Heme-oxygenase-1 attenuates oxidative functions of antigen presenting cells and promotes regulatory t cell differentiation during fasciola hepatica infection; Multidisciplinary Digital Publishing Institute; Antioxidants; 10; 12; 12-2021; 1-21
2076-3921
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2076-3921/10/12/1938
info:eu-repo/semantics/altIdentifier/doi/10.3390/antiox10121938
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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 13.22299

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