Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection

The larval stage of Echinococcus granulosus causes the chronic infection known as cystic echinococcosis, deploying strong inhibitory mechanisms on host immune responses. Using experimental intraperitoneal infection in C57BL/6 mice, we carried out an in-depth analysis of the local changes in macropha...

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Main Author: Grezzi, Leticia (author)
Other Authors: Martínez, Yamila E. (author), Barrios, Anabella A. (author), Díaz, Álvaro (author), Casaravilla, Cecilia (author)
Format: article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/20.500.12008/50897
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author Grezzi, Leticia
author2 Martínez, Yamila E.
Barrios, Anabella A.
Díaz, Álvaro
Casaravilla, Cecilia
author2_role author
author
author
author
author_browse Barrios, Anabella A.
Casaravilla, Cecilia
Díaz, Álvaro
Grezzi, Leticia
Martínez, Yamila E.
author_facet Grezzi, Leticia
Martínez, Yamila E.
Barrios, Anabella A.
Díaz, Álvaro
Casaravilla, Cecilia
author_role author
collection COLIBRI
dc.contributor.none.fl_str_mv Grezzi Leticia, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Inmunología
Martínez Yamila E., Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Inmunología
Barrios Anabella A., Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Inmunología
Díaz Álvaro, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Inmunología
Casaravilla Cecilia, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Inmunología
dc.creator.none.fl_str_mv Grezzi, Leticia
Martínez, Yamila E.
Barrios, Anabella A.
Díaz, Álvaro
Casaravilla, Cecilia
dc.date.none.fl_str_mv 2024
2025-08-04T17:59:50Z
2025-08-04T17:59:50Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv GREZZI, L., MARTÍNEZ, YE., BARRIOS, AA., y otros. Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection. Infect Immun [en línea] 2024, 92(2). DOI: 10.1128/iai.00276-23
https://hdl.handle.net/20.500.12008/50897
10.1128/iai.00276-23
dc.language.none.fl_str_mv en
eng
dc.relation.none.fl_str_mv Infect Immun. 92(2), 2024
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Licencia Creative Commons Atribución (CC - By 4.0)
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.none.fl_str_mv Echinococcus granulosus
M2-like macrophage
PD-L1/PD-L2
Immunosuppression
dc.title.none.fl_str_mv Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection
dc.type.none.fl_str_mv Artículo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
description The larval stage of Echinococcus granulosus causes the chronic infection known as cystic echinococcosis, deploying strong inhibitory mechanisms on host immune responses. Using experimental intraperitoneal infection in C57BL/6 mice, we carried out an in-depth analysis of the local changes in macrophage populations associated with chronic infection. In addition, we analyzed T cells and relevant soluble mediators. Infected animals showed an increase in local cell numbers, mostly accounted for by eosinophils, T cells, and macrophages. Within macrophage populations, the largest increases in cell numbers corresponded to resident large peritoneal macrophages (LPM). Monocyte recruitment appeared to be active, as judged by the increased number of monocytes and cells in the process of differentiation towards LPM, including small (SPM) and converting peritoneal macrophages (CPM). In contrast, we found no evidence of macrophage proliferation. Infection induced the expression of M2 markers in SPM, CPM, and LPM. It also enhanced the expression of the co-inhibitor PD-L1 in LPM, SPM, and CPM and induced the co-inhibitor PD-L2 in SPM and CPM. Therefore, local macrophages acquire M2-like phenotypes with probable suppressive capacities. Regarding T cells, infection induced an increase in the percentage of CD4+ cells that are PD-1+ , which represent a potential target of suppression by PD-L1+ /PD-L2+ macrophages. In possible agreement, CD4+ T cells from infected animals showed blunted proliferative responses to in vitro stimulation with anti-CD3. Further evidence of immune suppression in the parasite vicinity arose from the observation of an expansion in FoxP3+ CD4+ regulatory T cells and increases in the local concentrations of the anti-inflammatory cytokines TGF-β and IL-1Ra.
eu_rights_str_mv openAccess
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id anni_d84aaff5977b2a0911efc1d0a1f0e84f
identifier_str_mv GREZZI, L., MARTÍNEZ, YE., BARRIOS, AA., y otros. Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection. Infect Immun [en línea] 2024, 92(2). DOI: 10.1128/iai.00276-23
10.1128/iai.00276-23
instacron_str Universidad de la República
institution Universidad de la República
instname_str Universidad de la República
language eng
language_invalid_str_mv en
network_acronym_str anni
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oai_identifier_str oai:colibri.udelar.edu.uy:20.500.12008/50897
publishDate 2024
publishDateSort 2024
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rights_invalid_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
spelling Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infectionGrezzi, LeticiaMartínez, Yamila E.Barrios, Anabella A.Díaz, ÁlvaroCasaravilla, CeciliaEchinococcus granulosusM2-like macrophagePD-L1/PD-L2ImmunosuppressionThe larval stage of Echinococcus granulosus causes the chronic infection known as cystic echinococcosis, deploying strong inhibitory mechanisms on host immune responses. Using experimental intraperitoneal infection in C57BL/6 mice, we carried out an in-depth analysis of the local changes in macrophage populations associated with chronic infection. In addition, we analyzed T cells and relevant soluble mediators. Infected animals showed an increase in local cell numbers, mostly accounted for by eosinophils, T cells, and macrophages. Within macrophage populations, the largest increases in cell numbers corresponded to resident large peritoneal macrophages (LPM). Monocyte recruitment appeared to be active, as judged by the increased number of monocytes and cells in the process of differentiation towards LPM, including small (SPM) and converting peritoneal macrophages (CPM). In contrast, we found no evidence of macrophage proliferation. Infection induced the expression of M2 markers in SPM, CPM, and LPM. It also enhanced the expression of the co-inhibitor PD-L1 in LPM, SPM, and CPM and induced the co-inhibitor PD-L2 in SPM and CPM. Therefore, local macrophages acquire M2-like phenotypes with probable suppressive capacities. Regarding T cells, infection induced an increase in the percentage of CD4+ cells that are PD-1+ , which represent a potential target of suppression by PD-L1+ /PD-L2+ macrophages. In possible agreement, CD4+ T cells from infected animals showed blunted proliferative responses to in vitro stimulation with anti-CD3. Further evidence of immune suppression in the parasite vicinity arose from the observation of an expansion in FoxP3+ CD4+ regulatory T cells and increases in the local concentrations of the anti-inflammatory cytokines TGF-β and IL-1Ra.Comisión Sectorial de Investigación Científica (CSIC)Agencia Nacional de Investigación e Innovación (ANII)Grezzi Leticia, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica InmunologíaMartínez Yamila E., Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica InmunologíaBarrios Anabella A., Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica InmunologíaDíaz Álvaro, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica InmunologíaCasaravilla Cecilia, Universidad de la República (Uruguay). Facultad de Medicina. Instituto de Higiene. Unidad Académica Inmunología2025-08-04T17:59:50Z2025-08-04T17:59:50Z2024Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfGREZZI, L., MARTÍNEZ, YE., BARRIOS, AA., y otros. Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection. Infect Immun [en línea] 2024, 92(2). DOI: 10.1128/iai.00276-23https://hdl.handle.net/20.500.12008/5089710.1128/iai.00276-23reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengInfect Immun. 92(2), 2024Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/508972026-04-14T10:37:03Z
spellingShingle Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection
Grezzi, Leticia
Echinococcus granulosus
M2-like macrophage
PD-L1/PD-L2
Immunosuppression
status_str publishedVersion
title Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection
title_full Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection
title_fullStr Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection
title_full_unstemmed Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection
title_short Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection
title_sort Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection
topic Echinococcus granulosus
M2-like macrophage
PD-L1/PD-L2
Immunosuppression
url https://hdl.handle.net/20.500.12008/50897