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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| Format: | article |
| Language: | English |
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2024
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| Online Access: | https://hdl.handle.net/20.500.12008/50897 |
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| _version_ | 1868890205502570496 |
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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 |
| format | article |
| 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 |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/50897 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| reponame_str | COLIBRI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| 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 |