Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response.
Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditar...
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| Language: | English |
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Public Library of Science (PLoS)
2016-03-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005935&type=printable |
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| author | Luisa Ojeda-Fernández Lucía Recio-Poveda Mikel Aristorena Pedro Lastres Francisco J Blanco Francisco Sanz-Rodríguez Eunate Gallardo-Vara Mateo de las Casas-Engel Ángel Corbí Helen M Arthur Carmelo Bernabeu Luisa M Botella |
| author_facet | Luisa Ojeda-Fernández Lucía Recio-Poveda Mikel Aristorena Pedro Lastres Francisco J Blanco Francisco Sanz-Rodríguez Eunate Gallardo-Vara Mateo de las Casas-Engel Ángel Corbí Helen M Arthur Carmelo Bernabeu Luisa M Botella |
| author_sort | Luisa Ojeda-Fernández |
| collection | DOAJ |
| description | Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-Osler-Weber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Eng(fl/fl)LysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Eng(fl/fl)LysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients. |
| format | Article |
| id | doaj-art-63f0aca66e9c4e4a90b3922a52eccf65 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2016-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-63f0aca66e9c4e4a90b3922a52eccf652025-08-20T02:03:17ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-03-01123e100593510.1371/journal.pgen.1005935Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response.Luisa Ojeda-FernándezLucía Recio-PovedaMikel AristorenaPedro LastresFrancisco J BlancoFrancisco Sanz-RodríguezEunate Gallardo-VaraMateo de las Casas-EngelÁngel CorbíHelen M ArthurCarmelo BernabeuLuisa M BotellaEndoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-Osler-Weber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Eng(fl/fl)LysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Eng(fl/fl)LysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005935&type=printable |
| spellingShingle | Luisa Ojeda-Fernández Lucía Recio-Poveda Mikel Aristorena Pedro Lastres Francisco J Blanco Francisco Sanz-Rodríguez Eunate Gallardo-Vara Mateo de las Casas-Engel Ángel Corbí Helen M Arthur Carmelo Bernabeu Luisa M Botella Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response. PLoS Genetics |
| title | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response. |
| title_full | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response. |
| title_fullStr | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response. |
| title_full_unstemmed | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response. |
| title_short | Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response. |
| title_sort | mice lacking endoglin in macrophages show an impaired immune response |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005935&type=printable |
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