PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection

Autores
Stempin, Cinthia; Motran, Claudia Cristina; Aoki, Maria del Pilar; Falcón, Cristian Roberto; Cerban, Fabio Marcelo; Cervi, Laura Alejandra
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Macrophage plasticity is critical for controlling inflammation including thoseproduced by helminth infections, where alternatively activated macrophages (AAM)are accumulated in tissues. AAM expressing the co-inhibitory molecule programmeddeath ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasiticinfections. However, the role of PD-L2 during F. hepatica infection has not yet beenexplored. We observed that F. hepatica infection or a F. hepatica total extract (TE)injection increased the expression of PD-L2 on peritoneal macrophages. In addition,the absence of PD-L2 expression correlated with an increase in susceptibility to F.hepatica infection, as evidenced by the shorter survival and increased liver damageobserved in PD-L2 deficient (KO) mice. We assessed the contribution of the PD-L2pathway to Th2 polarization during this infection, and found that the absence of PD-L2caused a diminished Th2 type cytokine production by TE stimulated splenocytes fromPD-L2 KO infected compared with WT mice. Besides, splenocytes and intrahepaticleukocytes from infected PD-L2 KO mice showed higher levels of IFN-γ than thosefrom WT mice. Arginase expression and activity and IL-10 production were reducedin macrophages from PD-L2 KO mice compared to those from WT mice, revealing astrong correlation between PD-L2 expression and AAM polarization. Taken together,our data indicate that PD-L2 expression in macrophages is critical for AAM inductionand the maintenance of an optimal balance between the Th1- and Th2-type immuneresponses to assure host survival during F. hepatica infection.
Fil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Motran, Claudia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Falcón, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cerban, Fabio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
Macrophagemacrophage
Pd-L2
F. Hepatica
Th1 Response
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:11336/48357
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/48357
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infectionStempin, CinthiaMotran, Claudia CristinaAoki, Maria del PilarFalcón, Cristian RobertoCerban, Fabio MarceloCervi, Laura AlejandraMacrophagemacrophagePd-L2F. HepaticaTh1 Responsehttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Macrophage plasticity is critical for controlling inflammation including thoseproduced by helminth infections, where alternatively activated macrophages (AAM)are accumulated in tissues. AAM expressing the co-inhibitory molecule programmeddeath ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasiticinfections. However, the role of PD-L2 during F. hepatica infection has not yet beenexplored. We observed that F. hepatica infection or a F. hepatica total extract (TE)injection increased the expression of PD-L2 on peritoneal macrophages. In addition,the absence of PD-L2 expression correlated with an increase in susceptibility to F.hepatica infection, as evidenced by the shorter survival and increased liver damageobserved in PD-L2 deficient (KO) mice. We assessed the contribution of the PD-L2pathway to Th2 polarization during this infection, and found that the absence of PD-L2caused a diminished Th2 type cytokine production by TE stimulated splenocytes fromPD-L2 KO infected compared with WT mice. Besides, splenocytes and intrahepaticleukocytes from infected PD-L2 KO mice showed higher levels of IFN-γ than thosefrom WT mice. Arginase expression and activity and IL-10 production were reducedin macrophages from PD-L2 KO mice compared to those from WT mice, revealing astrong correlation between PD-L2 expression and AAM polarization. Taken together,our data indicate that PD-L2 expression in macrophages is critical for AAM inductionand the maintenance of an optimal balance between the Th1- and Th2-type immuneresponses to assure host survival during F. hepatica infection.Fil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Motran, Claudia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Falcón, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cerban, Fabio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaKarger2016-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/48357Stempin, Cinthia; Motran, Claudia Cristina; Aoki, Maria del Pilar; Falcón, Cristian Roberto; Cerban, Fabio Marcelo; et al.; PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection; Karger; Oncotarget; 7; 47; 10-2016; 77721-777311949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/27783986info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.12790info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:52:11Zoai:ri.conicet.gov.ar:11336/48357instacron: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:34982025-11-12 09:52:12.096CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection
title PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection
spellingShingle PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection
Stempin, Cinthia
Macrophagemacrophage
Pd-L2
F. Hepatica
Th1 Response
title_short PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection
title_full PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection
title_fullStr PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection
title_full_unstemmed PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection
title_sort PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection
dc.creator.none.fl_str_mv Stempin, Cinthia
Motran, Claudia Cristina
Aoki, Maria del Pilar
Falcón, Cristian Roberto
Cerban, Fabio Marcelo
Cervi, Laura Alejandra
author Stempin, Cinthia
author_facet Stempin, Cinthia
Motran, Claudia Cristina
Aoki, Maria del Pilar
Falcón, Cristian Roberto
Cerban, Fabio Marcelo
Cervi, Laura Alejandra
author_role author
author2 Motran, Claudia Cristina
Aoki, Maria del Pilar
Falcón, Cristian Roberto
Cerban, Fabio Marcelo
Cervi, Laura Alejandra
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Macrophagemacrophage
Pd-L2
F. Hepatica
Th1 Response
topic Macrophagemacrophage
Pd-L2
F. Hepatica
Th1 Response
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Macrophage plasticity is critical for controlling inflammation including thoseproduced by helminth infections, where alternatively activated macrophages (AAM)are accumulated in tissues. AAM expressing the co-inhibitory molecule programmeddeath ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasiticinfections. However, the role of PD-L2 during F. hepatica infection has not yet beenexplored. We observed that F. hepatica infection or a F. hepatica total extract (TE)injection increased the expression of PD-L2 on peritoneal macrophages. In addition,the absence of PD-L2 expression correlated with an increase in susceptibility to F.hepatica infection, as evidenced by the shorter survival and increased liver damageobserved in PD-L2 deficient (KO) mice. We assessed the contribution of the PD-L2pathway to Th2 polarization during this infection, and found that the absence of PD-L2caused a diminished Th2 type cytokine production by TE stimulated splenocytes fromPD-L2 KO infected compared with WT mice. Besides, splenocytes and intrahepaticleukocytes from infected PD-L2 KO mice showed higher levels of IFN-γ than thosefrom WT mice. Arginase expression and activity and IL-10 production were reducedin macrophages from PD-L2 KO mice compared to those from WT mice, revealing astrong correlation between PD-L2 expression and AAM polarization. Taken together,our data indicate that PD-L2 expression in macrophages is critical for AAM inductionand the maintenance of an optimal balance between the Th1- and Th2-type immuneresponses to assure host survival during F. hepatica infection.
Fil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Motran, Claudia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Falcón, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cerban, Fabio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Macrophage plasticity is critical for controlling inflammation including thoseproduced by helminth infections, where alternatively activated macrophages (AAM)are accumulated in tissues. AAM expressing the co-inhibitory molecule programmeddeath ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasiticinfections. However, the role of PD-L2 during F. hepatica infection has not yet beenexplored. We observed that F. hepatica infection or a F. hepatica total extract (TE)injection increased the expression of PD-L2 on peritoneal macrophages. In addition,the absence of PD-L2 expression correlated with an increase in susceptibility to F.hepatica infection, as evidenced by the shorter survival and increased liver damageobserved in PD-L2 deficient (KO) mice. We assessed the contribution of the PD-L2pathway to Th2 polarization during this infection, and found that the absence of PD-L2caused a diminished Th2 type cytokine production by TE stimulated splenocytes fromPD-L2 KO infected compared with WT mice. Besides, splenocytes and intrahepaticleukocytes from infected PD-L2 KO mice showed higher levels of IFN-γ than thosefrom WT mice. Arginase expression and activity and IL-10 production were reducedin macrophages from PD-L2 KO mice compared to those from WT mice, revealing astrong correlation between PD-L2 expression and AAM polarization. Taken together,our data indicate that PD-L2 expression in macrophages is critical for AAM inductionand the maintenance of an optimal balance between the Th1- and Th2-type immuneresponses to assure host survival during F. hepatica infection.
publishDate 2016
dc.date.none.fl_str_mv 2016-10
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/11336/48357
Stempin, Cinthia; Motran, Claudia Cristina; Aoki, Maria del Pilar; Falcón, Cristian Roberto; Cerban, Fabio Marcelo; et al.; PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection; Karger; Oncotarget; 7; 47; 10-2016; 77721-77731
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48357
identifier_str_mv Stempin, Cinthia; Motran, Claudia Cristina; Aoki, Maria del Pilar; Falcón, Cristian Roberto; Cerban, Fabio Marcelo; et al.; PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection; Karger; Oncotarget; 7; 47; 10-2016; 77721-77731
1949-2553
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.ncbi.nlm.nih.gov/pubmed/27783986
info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.12790
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
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Karger
publisher.none.fl_str_mv Karger
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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