SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability
SARS-CoV-2 is a devastating virus that induces a range of immunopathological mechanisms including cytokine storm, apoptosis, inflammation and complement and coagulation pathway hyperactivation. However, how the infection impacts pregnant mothers is still being worked out due to evidence of vertical...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.957224/full |
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| author | Chiara Agostinis Miriam Toffoli Mariagiulia Spazzapan Andrea Balduit Gabriella Zito Alessandro Mangogna Luisa Zupin Tiziana Salviato Serena Maiocchi Serena Maiocchi Federico Romano Sergio Crovella Francesco Fontana Luca Braga Marco Confalonieri Giuseppe Ricci Giuseppe Ricci Uday Kishore Uday Kishore Roberta Bulla |
| author_facet | Chiara Agostinis Miriam Toffoli Mariagiulia Spazzapan Andrea Balduit Gabriella Zito Alessandro Mangogna Luisa Zupin Tiziana Salviato Serena Maiocchi Serena Maiocchi Federico Romano Sergio Crovella Francesco Fontana Luca Braga Marco Confalonieri Giuseppe Ricci Giuseppe Ricci Uday Kishore Uday Kishore Roberta Bulla |
| author_sort | Chiara Agostinis |
| collection | DOAJ |
| description | SARS-CoV-2 is a devastating virus that induces a range of immunopathological mechanisms including cytokine storm, apoptosis, inflammation and complement and coagulation pathway hyperactivation. However, how the infection impacts pregnant mothers is still being worked out due to evidence of vertical transmission of the SARS-CoV-2, and higher incidence of pre-eclampsia, preterm birth, caesarian section, and fetal mortality. In this study, we assessed the levels of the three main receptors of SARS-CoV-2 (ACE2, TMPRSS2 and CD147) in placentae derived from SARS-CoV-2 positive and negative mothers. Moreover, we measured the effects of Spike protein on placental cell lines, in addition to their susceptibility to infection. SARS-CoV-2 negative placentae showed elevated levels of CD147 and considerably low amount of TMPRSS2, making them non-permissive to infection. SARS-CoV-2 presence upregulated TMPRSS2 expression in syncytiotrophoblast and cytotrophoblast cells, thereby rendering them amenable to infection. The non-permissiveness of placental cells can be due to their less fusogenicity due to infection. We also found that Spike protein was capable of inducing pro-inflammatory cytokine production, syncytiotrophoblast apoptosis and increased vascular permeability. These events can elicit pre-eclampsia-like syndrome that marks a high percentage of pregnancies when mothers are infected with SARS-CoV-2. Our study raises important points relevant to SARS-CoV-2 mediated adverse pregnancy outcomes. |
| first_indexed | 2024-04-12T04:42:04Z |
| format | Article |
| id | doaj.art-3da646b16b6e46148e36e3ce36c4ad36 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T04:42:04Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3da646b16b6e46148e36e3ce36c4ad362022-12-22T03:47:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.957224957224SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeabilityChiara Agostinis0Miriam Toffoli1Mariagiulia Spazzapan2Andrea Balduit3Gabriella Zito4Alessandro Mangogna5Luisa Zupin6Tiziana Salviato7Serena Maiocchi8Serena Maiocchi9Federico Romano10Sergio Crovella11Francesco Fontana12Luca Braga13Marco Confalonieri14Giuseppe Ricci15Giuseppe Ricci16Uday Kishore17Uday Kishore18Roberta Bulla19Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, ItalyInstitute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyInstitute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, ItalyInstitute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, ItalyInstitute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, ItalyInstitute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, ItalyDepartment of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyFunctional Cell Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyInstitute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, ItalyBiological Science Program, Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, QatarDivision of Laboratory Medicine, Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI), Trieste, ItalyFunctional Cell Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, Trieste, ItalyInstitute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, Trieste, ItalyBiosciences, College of Health, Medicine and Life Sciences, Brunel University of London, London, United KingdomDepartment of Veterinary Medicine, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Life Sciences, University of Trieste, Trieste, ItalySARS-CoV-2 is a devastating virus that induces a range of immunopathological mechanisms including cytokine storm, apoptosis, inflammation and complement and coagulation pathway hyperactivation. However, how the infection impacts pregnant mothers is still being worked out due to evidence of vertical transmission of the SARS-CoV-2, and higher incidence of pre-eclampsia, preterm birth, caesarian section, and fetal mortality. In this study, we assessed the levels of the three main receptors of SARS-CoV-2 (ACE2, TMPRSS2 and CD147) in placentae derived from SARS-CoV-2 positive and negative mothers. Moreover, we measured the effects of Spike protein on placental cell lines, in addition to their susceptibility to infection. SARS-CoV-2 negative placentae showed elevated levels of CD147 and considerably low amount of TMPRSS2, making them non-permissive to infection. SARS-CoV-2 presence upregulated TMPRSS2 expression in syncytiotrophoblast and cytotrophoblast cells, thereby rendering them amenable to infection. The non-permissiveness of placental cells can be due to their less fusogenicity due to infection. We also found that Spike protein was capable of inducing pro-inflammatory cytokine production, syncytiotrophoblast apoptosis and increased vascular permeability. These events can elicit pre-eclampsia-like syndrome that marks a high percentage of pregnancies when mothers are infected with SARS-CoV-2. Our study raises important points relevant to SARS-CoV-2 mediated adverse pregnancy outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2022.957224/fullSARS-CoV-2ACE2TMPRSS2CD147pregnancy |
| spellingShingle | Chiara Agostinis Miriam Toffoli Mariagiulia Spazzapan Andrea Balduit Gabriella Zito Alessandro Mangogna Luisa Zupin Tiziana Salviato Serena Maiocchi Serena Maiocchi Federico Romano Sergio Crovella Francesco Fontana Luca Braga Marco Confalonieri Giuseppe Ricci Giuseppe Ricci Uday Kishore Uday Kishore Roberta Bulla SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability Frontiers in Immunology SARS-CoV-2 ACE2 TMPRSS2 CD147 pregnancy |
| title | SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability |
| title_full | SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability |
| title_fullStr | SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability |
| title_full_unstemmed | SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability |
| title_short | SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability |
| title_sort | sars cov 2 modulates virus receptor expression in placenta and can induce trophoblast fusion inflammation and endothelial permeability |
| topic | SARS-CoV-2 ACE2 TMPRSS2 CD147 pregnancy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.957224/full |
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