High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice
In the course of atherogenesis, the spleen plays an important role in the regulation of extramedullary hematopoiesis, and in the control of circulating immune cells, which contributes to plaque progression. Here, we have investigated the role of splenic nucleotide-binding oligomerization domain 1 (N...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/283866 |
| Acceso en línea: | http://hdl.handle.net/10261/283866 |
| Access Level: | acceso abierto |
| Palabra clave: | Spleen NETosis Hypercholesterolemia Atherogenesis Partial splenectomy |
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High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice |
| title |
High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice |
| spellingShingle |
High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice Fernández-García, Victoria Spleen NETosis Hypercholesterolemia Atherogenesis Partial splenectomy |
| title_short |
High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice |
| title_full |
High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice |
| title_fullStr |
High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice |
| title_full_unstemmed |
High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice |
| title_sort |
High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice |
| dc.creator.none.fl_str_mv |
Fernández-García, Victoria González-Ramos, Silvia Avendaño-Ortiz, José Martín-Sanz, Paloma Gómez-Coronado, Diego Delgado, Carmen Castrillo, Antonio Boscá, Lisardo |
| author |
Fernández-García, Victoria |
| author_facet |
Fernández-García, Victoria González-Ramos, Silvia Avendaño-Ortiz, José Martín-Sanz, Paloma Gómez-Coronado, Diego Delgado, Carmen Castrillo, Antonio Boscá, Lisardo |
| author_role |
author |
| author2 |
González-Ramos, Silvia Avendaño-Ortiz, José Martín-Sanz, Paloma Gómez-Coronado, Diego Delgado, Carmen Castrillo, Antonio Boscá, Lisardo |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Ciencia, Innovación y Universidades (España) Agencia Estatal de Investigación (España) Centro Nacional de Investigaciones Cardiovasculares (España) Comunidad de Madrid European Commission Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Spleen NETosis Hypercholesterolemia Atherogenesis Partial splenectomy |
| topic |
Spleen NETosis Hypercholesterolemia Atherogenesis Partial splenectomy |
| description |
In the course of atherogenesis, the spleen plays an important role in the regulation of extramedullary hematopoiesis, and in the control of circulating immune cells, which contributes to plaque progression. Here, we have investigated the role of splenic nucleotide-binding oligomerization domain 1 (NOD1) in the recruitment of circulating immune cells, as well as the involvement of this immune organ in extramedullary hematopoiesis in mice fed on a high-fat high-cholesterol diet (HFD). Under HFD conditions, the absence of NOD1 enhances the mobilization of immune cells, mainly neutrophils, from the bone marrow to the blood. To determine the effect of NOD1-dependent mobilization of immune cells under pro-atherogenic conditions, Apoe−/− and Apoe−/−Nod1−/− mice fed on HFD for 4 weeks were used. Splenic NOD1 from Apoe−/− mice was activated after feeding HFD as inferred by the phosphorylation of the NOD1 downstream targets RIPK2 and TAK1. Moreover, this activation was accompanied by the release of neutrophil extracellular traps (NETs), as determined by the increase in the expression of peptidyl arginine deiminase 4, and the identification of citrullinated histone H3 in this organ. This formation of NETs was significantly reduced in Apoe−/−Nod1−/− mice. Indeed, the presence of Ly6G+ cells and the lipidic content in the spleen of mice deficient in Apoe and Nod1 was reduced when compared to the Apoe−/− counterparts, which suggests that the mobilization and activation of circulating immune cells are altered in the absence of NOD1. Furthermore, confirming previous studies, Apoe−/−Nod1−/− mice showed a reduced atherogenic disease, and diminished recruitment of neutrophils in the spleen, compared to Apoe−/− mice. However, splenic artery ligation reduced the atherogenic burden in Apoe−/− mice an effect that, unexpectedly was lost in Apoe−/−Nod1−/− mice. Together, these results suggest that neutrophil accumulation and activity in the spleen are driven in part by NOD1 activation in mice fed on HFD, contributing in this way to regulating atherogenic progression. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022 2022 2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10261/283866 |
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http://hdl.handle.net/10261/283866 |
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Inglés |
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openAccess |
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application/pdf |
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Birkhäuser Verlag Springer Nature |
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Birkhäuser Verlag Springer Nature |
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High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient miceFernández-García, VictoriaGonzález-Ramos, SilviaAvendaño-Ortiz, JoséMartín-Sanz, PalomaGómez-Coronado, DiegoDelgado, CarmenCastrillo, AntonioBoscá, LisardoSpleenNETosisHypercholesterolemiaAtherogenesisPartial splenectomyIn the course of atherogenesis, the spleen plays an important role in the regulation of extramedullary hematopoiesis, and in the control of circulating immune cells, which contributes to plaque progression. Here, we have investigated the role of splenic nucleotide-binding oligomerization domain 1 (NOD1) in the recruitment of circulating immune cells, as well as the involvement of this immune organ in extramedullary hematopoiesis in mice fed on a high-fat high-cholesterol diet (HFD). Under HFD conditions, the absence of NOD1 enhances the mobilization of immune cells, mainly neutrophils, from the bone marrow to the blood. To determine the effect of NOD1-dependent mobilization of immune cells under pro-atherogenic conditions, Apoe−/− and Apoe−/−Nod1−/− mice fed on HFD for 4 weeks were used. Splenic NOD1 from Apoe−/− mice was activated after feeding HFD as inferred by the phosphorylation of the NOD1 downstream targets RIPK2 and TAK1. Moreover, this activation was accompanied by the release of neutrophil extracellular traps (NETs), as determined by the increase in the expression of peptidyl arginine deiminase 4, and the identification of citrullinated histone H3 in this organ. This formation of NETs was significantly reduced in Apoe−/−Nod1−/− mice. Indeed, the presence of Ly6G+ cells and the lipidic content in the spleen of mice deficient in Apoe and Nod1 was reduced when compared to the Apoe−/− counterparts, which suggests that the mobilization and activation of circulating immune cells are altered in the absence of NOD1. Furthermore, confirming previous studies, Apoe−/−Nod1−/− mice showed a reduced atherogenic disease, and diminished recruitment of neutrophils in the spleen, compared to Apoe−/− mice. However, splenic artery ligation reduced the atherogenic burden in Apoe−/− mice an effect that, unexpectedly was lost in Apoe−/−Nod1−/− mice. Together, these results suggest that neutrophil accumulation and activity in the spleen are driven in part by NOD1 activation in mice fed on HFD, contributing in this way to regulating atherogenic progression.This work has been supported by: Ministerio de Ciencia, Investigación y Universidades, Agencia Estatal de Investigación *** (PID2019-104284RB-I00, PID2020-113238RB-I00, RTI2018-098113B-I00, PID2019-108977RB-I00), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222) and Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686, Fondo Social Europeo and Fondo Europeo de Desarrollo Regional.Birkhäuser VerlagSpringer NatureMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Centro Nacional de Investigaciones Cardiovasculares (España)Comunidad de MadridEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/283866reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104284RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113238RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098113-B-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-108977RB-I00S2017/BMD-3686http://dx.doi.org/10.1007/s00018-022-04415-xSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2838662026-05-22T06:33:51Z |
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