Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages
Abstract Background Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that int...
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BMC
2024-10-01
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| Series: | Biology of Sex Differences |
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| Online Access: | https://doi.org/10.1186/s13293-024-00652-w |
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| author | Daniel E. Paparini Esteban Grasso Franco Aguilera M. Agustina Arslanian Victoria Lella Brenda Lara Ana Schafir Soledad Gori Fátima Merech Vanesa Hauk Claudio Schuster Marcelo Martí Cesar Meller Rosanna Ramhorst Daiana Vota Claudia Pérez Leirós |
| author_facet | Daniel E. Paparini Esteban Grasso Franco Aguilera M. Agustina Arslanian Victoria Lella Brenda Lara Ana Schafir Soledad Gori Fátima Merech Vanesa Hauk Claudio Schuster Marcelo Martí Cesar Meller Rosanna Ramhorst Daiana Vota Claudia Pérez Leirós |
| author_sort | Daniel E. Paparini |
| collection | DOAJ |
| description | Abstract Background Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet. Here we studied the sex-specific differences in the phenotypic, functional and immunometabolic profile of HBC. Methods HBC were isolated from human term placentas (N = 31, 16 from male and 15 female neonates). Ex vivo assays were carried out to assess active metabolic and endoplasmic reticulum stress pathways by flow cytometry, confocal microscopy, gene expression and in silico approaches. Results HBC from female placentas displayed a stronger M2 phenotype accompanied by high rates of efferocytosis majorly sustained on lipid metabolism. On the other hand, male HBC expressed a weaker M2 phenotype with higher glycolytic metabolism. LPS stimulation reinforced the glycolytic metabolism in male but not in female HBC. Physiological endoplasmic reticulum stress activates IRE-1 differently, since its pharmacological inhibition increased lipid mobilization, accumulation and efferocytosis only in female HBC. Moreover, differential sex-associated pathways accompanying the phenotypic and functional profiles of HBC appeared related to the placental villi environment. Conclusions These results support sex-associated effects on the immunometabolism of the HBC and adds another layer of complexity to the intricate maternal-fetal immune interaction. Graphical abstract |
| format | Article |
| id | doaj-art-87b951a1dc6c453d813d1a0e28471877 |
| institution | OA Journals |
| issn | 2042-6410 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj-art-87b951a1dc6c453d813d1a0e284718772025-08-20T02:17:34ZengBMCBiology of Sex Differences2042-64102024-10-0115111410.1186/s13293-024-00652-wSex-specific phenotypical, functional and metabolic profiles of human term placenta macrophagesDaniel E. Paparini0Esteban Grasso1Franco Aguilera2M. Agustina Arslanian3Victoria Lella4Brenda Lara5Ana Schafir6Soledad Gori7Fátima Merech8Vanesa Hauk9Claudio Schuster10Marcelo Martí11Cesar Meller12Rosanna Ramhorst13Daiana Vota14Claudia Pérez Leirós15Immunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Immunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Immunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Obstetric Service, Hospital ItalianoObstetric Service, Hospital ItalianoImmunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Immunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Immunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Immunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Immunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Bioinformatic Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Bioinformatic Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Obstetric Service, Hospital ItalianoImmunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Immunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Immunopharmacology Laboratory, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Abstract Background Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet. Here we studied the sex-specific differences in the phenotypic, functional and immunometabolic profile of HBC. Methods HBC were isolated from human term placentas (N = 31, 16 from male and 15 female neonates). Ex vivo assays were carried out to assess active metabolic and endoplasmic reticulum stress pathways by flow cytometry, confocal microscopy, gene expression and in silico approaches. Results HBC from female placentas displayed a stronger M2 phenotype accompanied by high rates of efferocytosis majorly sustained on lipid metabolism. On the other hand, male HBC expressed a weaker M2 phenotype with higher glycolytic metabolism. LPS stimulation reinforced the glycolytic metabolism in male but not in female HBC. Physiological endoplasmic reticulum stress activates IRE-1 differently, since its pharmacological inhibition increased lipid mobilization, accumulation and efferocytosis only in female HBC. Moreover, differential sex-associated pathways accompanying the phenotypic and functional profiles of HBC appeared related to the placental villi environment. Conclusions These results support sex-associated effects on the immunometabolism of the HBC and adds another layer of complexity to the intricate maternal-fetal immune interaction. Graphical abstracthttps://doi.org/10.1186/s13293-024-00652-wPlacental-macrophagesMetabolismSex-associated differences |
| spellingShingle | Daniel E. Paparini Esteban Grasso Franco Aguilera M. Agustina Arslanian Victoria Lella Brenda Lara Ana Schafir Soledad Gori Fátima Merech Vanesa Hauk Claudio Schuster Marcelo Martí Cesar Meller Rosanna Ramhorst Daiana Vota Claudia Pérez Leirós Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages Biology of Sex Differences Placental-macrophages Metabolism Sex-associated differences |
| title | Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages |
| title_full | Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages |
| title_fullStr | Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages |
| title_full_unstemmed | Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages |
| title_short | Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages |
| title_sort | sex specific phenotypical functional and metabolic profiles of human term placenta macrophages |
| topic | Placental-macrophages Metabolism Sex-associated differences |
| url | https://doi.org/10.1186/s13293-024-00652-w |
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