Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection

Autores
Carasi, Paula; Rodriguez, Ernesto; da Costa, Valeria; Frigerio, Sofía; Brossart, Natalie; Noya, Verónica; Robello, Carlos; Anegón, Ignacio; Freire, Teresa
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fasciola hepatica, also known as the liver fluke, is a trematode that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. This parasite immunoregulates the host immune system by inducing a strong Th2 and regulatory T immune response by immunomodulating dendritic cell (DC) maturation and alternative activation of macrophages. In this paper, we show that F. hepatica infection in mice induces the upregulation of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that regulates the host inflammatory response. We show and characterize two different populations of antigen presenting cells that express HO-1 during infection in the peritoneum of infected animals. Cells that expressed high levels of HO-1 expressed intermediate levels of F4/80 but high expression of CD11c, CD38, TGFβ, and IL-10 suggesting that they correspond to regulatory DCs. On the other hand, cells expressing intermediate levels of HO-1 expressed high levels of F4/80, CD68, Ly6C, and FIZZ-1, indicating that they might correspond to alternatively activated macrophages. Furthermore, the pharmacological induction of HO-1 with the synthetic metalloporphyrin CoPP promoted F. hepatica infection increasing the clinical signs associated with the disease. In contrast, treatment with the HO-1 inhibitor SnPP protected mice from parasite infection, indicating that HO-1 plays an essential role during F. hepatica infection. Finally, HO-1 expression during F. hepatica infection was associated with TGFβ and IL-10 levels in liver and peritoneum, suggesting that HO-1 controls the expression of these immunoregulatory cytokines during infection favoring parasite survival in the host. These results contribute to the elucidation of the immunoregulatory mechanisms induced by F. hepatica in the host and provide alternative checkpoints to control fasciolosis.
Fil: Carasi, Paula. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez, Ernesto. Universidad de la República; Uruguay
Fil: da Costa, Valeria. Universidad de la República; Uruguay
Fil: Frigerio, Sofía. Universidad de la República; Uruguay
Fil: Brossart, Natalie. Universidad de la República; Uruguay
Fil: Noya, Verónica. Universidad de la República; Uruguay
Fil: Robello, Carlos. Instituto Pasteur de Montevideo. Unidad de Biología Molecular; Uruguay
Fil: Anegón, Ignacio. Centre de Recherche de Nantes; Francia
Fil: Freire, Teresa. Universidad de la República; Uruguay
Materia
DENDRITIC CELL
HELMINTH
HEME-OXIGENASE-1
IMMUNE REGULATION
MACROPHAGE
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:11336/56789
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/56789
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infectionCarasi, PaulaRodriguez, Ernestoda Costa, ValeriaFrigerio, SofíaBrossart, NatalieNoya, VerónicaRobello, CarlosAnegón, IgnacioFreire, TeresaDENDRITIC CELLHELMINTHHEME-OXIGENASE-1IMMUNE REGULATIONMACROPHAGEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Fasciola hepatica, also known as the liver fluke, is a trematode that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. This parasite immunoregulates the host immune system by inducing a strong Th2 and regulatory T immune response by immunomodulating dendritic cell (DC) maturation and alternative activation of macrophages. In this paper, we show that F. hepatica infection in mice induces the upregulation of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that regulates the host inflammatory response. We show and characterize two different populations of antigen presenting cells that express HO-1 during infection in the peritoneum of infected animals. Cells that expressed high levels of HO-1 expressed intermediate levels of F4/80 but high expression of CD11c, CD38, TGFβ, and IL-10 suggesting that they correspond to regulatory DCs. On the other hand, cells expressing intermediate levels of HO-1 expressed high levels of F4/80, CD68, Ly6C, and FIZZ-1, indicating that they might correspond to alternatively activated macrophages. Furthermore, the pharmacological induction of HO-1 with the synthetic metalloporphyrin CoPP promoted F. hepatica infection increasing the clinical signs associated with the disease. In contrast, treatment with the HO-1 inhibitor SnPP protected mice from parasite infection, indicating that HO-1 plays an essential role during F. hepatica infection. Finally, HO-1 expression during F. hepatica infection was associated with TGFβ and IL-10 levels in liver and peritoneum, suggesting that HO-1 controls the expression of these immunoregulatory cytokines during infection favoring parasite survival in the host. These results contribute to the elucidation of the immunoregulatory mechanisms induced by F. hepatica in the host and provide alternative checkpoints to control fasciolosis.Fil: Carasi, Paula. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez, Ernesto. Universidad de la República; UruguayFil: da Costa, Valeria. Universidad de la República; UruguayFil: Frigerio, Sofía. Universidad de la República; UruguayFil: Brossart, Natalie. Universidad de la República; UruguayFil: Noya, Verónica. Universidad de la República; UruguayFil: Robello, Carlos. Instituto Pasteur de Montevideo. Unidad de Biología Molecular; UruguayFil: Anegón, Ignacio. Centre de Recherche de Nantes; FranciaFil: Freire, Teresa. Universidad de la República; UruguayFrontiers Research Foundation2017-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/56789Carasi, Paula; Rodriguez, Ernesto; da Costa, Valeria; Frigerio, Sofía; Brossart, Natalie; et al.; Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection; Frontiers Research Foundation; Frontiers in Immunology; 8; JUL; 7-2017; 1-151664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2017.00883info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2017.00883/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:43:41Zoai:ri.conicet.gov.ar:11336/56789instacron: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 15:43:42.062CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection
title Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection
spellingShingle Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection
Carasi, Paula
DENDRITIC CELL
HELMINTH
HEME-OXIGENASE-1
IMMUNE REGULATION
MACROPHAGE
title_short Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection
title_full Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection
title_fullStr Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection
title_full_unstemmed Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection
title_sort Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection
dc.creator.none.fl_str_mv Carasi, Paula
Rodriguez, Ernesto
da Costa, Valeria
Frigerio, Sofía
Brossart, Natalie
Noya, Verónica
Robello, Carlos
Anegón, Ignacio
Freire, Teresa
author Carasi, Paula
author_facet Carasi, Paula
Rodriguez, Ernesto
da Costa, Valeria
Frigerio, Sofía
Brossart, Natalie
Noya, Verónica
Robello, Carlos
Anegón, Ignacio
Freire, Teresa
author_role author
author2 Rodriguez, Ernesto
da Costa, Valeria
Frigerio, Sofía
Brossart, Natalie
Noya, Verónica
Robello, Carlos
Anegón, Ignacio
Freire, Teresa
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DENDRITIC CELL
HELMINTH
HEME-OXIGENASE-1
IMMUNE REGULATION
MACROPHAGE
topic DENDRITIC CELL
HELMINTH
HEME-OXIGENASE-1
IMMUNE REGULATION
MACROPHAGE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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, also known as the liver fluke, is a trematode that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. This parasite immunoregulates the host immune system by inducing a strong Th2 and regulatory T immune response by immunomodulating dendritic cell (DC) maturation and alternative activation of macrophages. In this paper, we show that F. hepatica infection in mice induces the upregulation of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that regulates the host inflammatory response. We show and characterize two different populations of antigen presenting cells that express HO-1 during infection in the peritoneum of infected animals. Cells that expressed high levels of HO-1 expressed intermediate levels of F4/80 but high expression of CD11c, CD38, TGFβ, and IL-10 suggesting that they correspond to regulatory DCs. On the other hand, cells expressing intermediate levels of HO-1 expressed high levels of F4/80, CD68, Ly6C, and FIZZ-1, indicating that they might correspond to alternatively activated macrophages. Furthermore, the pharmacological induction of HO-1 with the synthetic metalloporphyrin CoPP promoted F. hepatica infection increasing the clinical signs associated with the disease. In contrast, treatment with the HO-1 inhibitor SnPP protected mice from parasite infection, indicating that HO-1 plays an essential role during F. hepatica infection. Finally, HO-1 expression during F. hepatica infection was associated with TGFβ and IL-10 levels in liver and peritoneum, suggesting that HO-1 controls the expression of these immunoregulatory cytokines during infection favoring parasite survival in the host. These results contribute to the elucidation of the immunoregulatory mechanisms induced by F. hepatica in the host and provide alternative checkpoints to control fasciolosis.
Fil: Carasi, Paula. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez, Ernesto. Universidad de la República; Uruguay
Fil: da Costa, Valeria. Universidad de la República; Uruguay
Fil: Frigerio, Sofía. Universidad de la República; Uruguay
Fil: Brossart, Natalie. Universidad de la República; Uruguay
Fil: Noya, Verónica. Universidad de la República; Uruguay
Fil: Robello, Carlos. Instituto Pasteur de Montevideo. Unidad de Biología Molecular; Uruguay
Fil: Anegón, Ignacio. Centre de Recherche de Nantes; Francia
Fil: Freire, Teresa. Universidad de la República; Uruguay
description Fasciola hepatica, also known as the liver fluke, is a trematode that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. This parasite immunoregulates the host immune system by inducing a strong Th2 and regulatory T immune response by immunomodulating dendritic cell (DC) maturation and alternative activation of macrophages. In this paper, we show that F. hepatica infection in mice induces the upregulation of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that regulates the host inflammatory response. We show and characterize two different populations of antigen presenting cells that express HO-1 during infection in the peritoneum of infected animals. Cells that expressed high levels of HO-1 expressed intermediate levels of F4/80 but high expression of CD11c, CD38, TGFβ, and IL-10 suggesting that they correspond to regulatory DCs. On the other hand, cells expressing intermediate levels of HO-1 expressed high levels of F4/80, CD68, Ly6C, and FIZZ-1, indicating that they might correspond to alternatively activated macrophages. Furthermore, the pharmacological induction of HO-1 with the synthetic metalloporphyrin CoPP promoted F. hepatica infection increasing the clinical signs associated with the disease. In contrast, treatment with the HO-1 inhibitor SnPP protected mice from parasite infection, indicating that HO-1 plays an essential role during F. hepatica infection. Finally, HO-1 expression during F. hepatica infection was associated with TGFβ and IL-10 levels in liver and peritoneum, suggesting that HO-1 controls the expression of these immunoregulatory cytokines during infection favoring parasite survival in the host. These results contribute to the elucidation of the immunoregulatory mechanisms induced by F. hepatica in the host and provide alternative checkpoints to control fasciolosis.
publishDate 2017
dc.date.none.fl_str_mv 2017-07
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/11336/56789
Carasi, Paula; Rodriguez, Ernesto; da Costa, Valeria; Frigerio, Sofía; Brossart, Natalie; et al.; Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection; Frontiers Research Foundation; Frontiers in Immunology; 8; JUL; 7-2017; 1-15
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/56789
identifier_str_mv Carasi, Paula; Rodriguez, Ernesto; da Costa, Valeria; Frigerio, Sofía; Brossart, Natalie; et al.; Heme-oxygenase-1 expression contributes to the immunoregulation induced by Fasciola hepatica and promotes infection; Frontiers Research Foundation; Frontiers in Immunology; 8; JUL; 7-2017; 1-15
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2017.00883
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2017.00883/full
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 Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
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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