Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I Interferons
Recent evidence suggests that SARS-CoV-2 hinders immune responses via dopamine (DA)-related mechanisms. Nonetheless, studies addressing the specific role of DA in the frame of SARS-CoV-2 infection are still missing. In the present study, we investigate the role of DA in SARS-CoV-2 replication along...
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MDPI AG
2022-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/10/1691 |
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| author | Fiona Limanaqi Silvia Zecchini Borana Dino Sergio Strizzi Gioia Cappelletti Olga Utyro Claudia Vanetti Micaela Garziano Irma Saulle Mario Clerici Mara Biasin |
| author_facet | Fiona Limanaqi Silvia Zecchini Borana Dino Sergio Strizzi Gioia Cappelletti Olga Utyro Claudia Vanetti Micaela Garziano Irma Saulle Mario Clerici Mara Biasin |
| author_sort | Fiona Limanaqi |
| collection | DOAJ |
| description | Recent evidence suggests that SARS-CoV-2 hinders immune responses via dopamine (DA)-related mechanisms. Nonetheless, studies addressing the specific role of DA in the frame of SARS-CoV-2 infection are still missing. In the present study, we investigate the role of DA in SARS-CoV-2 replication along with potential links with innate immune pathways in CaLu-3 human epithelial lung cells. We document here for the first time that, besides DA synthetic pathways, SARS-CoV-2 alters the expression of D1 and D2 DA receptors (D1DR, D2DR), while DA administration reduces viral replication. Such an effect occurs at non-toxic, micromolar-range DA doses, which are known to induce receptor desensitization and downregulation. Indeed, the antiviral effects of DA were associated with a robust downregulation of D2DRs both at mRNA and protein levels, while the amount of D1DRs was not significantly affected. While halting SARS-CoV-2 replication, DA, similar to the D2DR agonist quinpirole, upregulates the expression of ISGs and Type-I IFNs, which goes along with the downregulation of various pro-inflammatory mediators. In turn, administration of Type-I IFNs, while dramatically reducing SARS-CoV-2 replication, converges in downregulating D2DRs expression. Besides configuring the CaLu-3 cell line as a suitable model to study SARS-CoV-2-induced alterations at the level of the DA system in the periphery, our findings disclose a previously unappreciated correlation between DA pathways and Type-I IFN response, which may be disrupted by SARS-CoV-2 for host cell invasion and replication. |
| first_indexed | 2024-03-10T03:09:18Z |
| format | Article |
| id | doaj.art-08018572dce84258a1cc03a33735bf07 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:09:18Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-08018572dce84258a1cc03a33735bf072023-11-23T10:28:16ZengMDPI AGCells2073-44092022-05-011110169110.3390/cells11101691Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I InterferonsFiona Limanaqi0Silvia Zecchini1Borana Dino2Sergio Strizzi3Gioia Cappelletti4Olga Utyro5Claudia Vanetti6Micaela Garziano7Irma Saulle8Mario Clerici9Mara Biasin10Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via G.B. Grassi, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via G.B. Grassi, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via G.B. Grassi, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via G.B. Grassi, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via G.B. Grassi, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via G.B. Grassi, 20122 Milan, ItalyDepartment of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via G.B. Grassi, 20122 Milan, ItalyDepartment of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza, 20122 Milan, ItalyDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via G.B. Grassi, 20122 Milan, ItalyRecent evidence suggests that SARS-CoV-2 hinders immune responses via dopamine (DA)-related mechanisms. Nonetheless, studies addressing the specific role of DA in the frame of SARS-CoV-2 infection are still missing. In the present study, we investigate the role of DA in SARS-CoV-2 replication along with potential links with innate immune pathways in CaLu-3 human epithelial lung cells. We document here for the first time that, besides DA synthetic pathways, SARS-CoV-2 alters the expression of D1 and D2 DA receptors (D1DR, D2DR), while DA administration reduces viral replication. Such an effect occurs at non-toxic, micromolar-range DA doses, which are known to induce receptor desensitization and downregulation. Indeed, the antiviral effects of DA were associated with a robust downregulation of D2DRs both at mRNA and protein levels, while the amount of D1DRs was not significantly affected. While halting SARS-CoV-2 replication, DA, similar to the D2DR agonist quinpirole, upregulates the expression of ISGs and Type-I IFNs, which goes along with the downregulation of various pro-inflammatory mediators. In turn, administration of Type-I IFNs, while dramatically reducing SARS-CoV-2 replication, converges in downregulating D2DRs expression. Besides configuring the CaLu-3 cell line as a suitable model to study SARS-CoV-2-induced alterations at the level of the DA system in the periphery, our findings disclose a previously unappreciated correlation between DA pathways and Type-I IFN response, which may be disrupted by SARS-CoV-2 for host cell invasion and replication.https://www.mdpi.com/2073-4409/11/10/1691dopamineD2DRinterferonsquinpiroleNLRP3 inflammasome |
| spellingShingle | Fiona Limanaqi Silvia Zecchini Borana Dino Sergio Strizzi Gioia Cappelletti Olga Utyro Claudia Vanetti Micaela Garziano Irma Saulle Mario Clerici Mara Biasin Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I Interferons Cells dopamine D2DR interferons quinpirole NLRP3 inflammasome |
| title | Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I Interferons |
| title_full | Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I Interferons |
| title_fullStr | Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I Interferons |
| title_full_unstemmed | Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I Interferons |
| title_short | Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I Interferons |
| title_sort | dopamine reduces sars cov 2 replication in vitro through downregulation of d2 receptors and upregulation of type i interferons |
| topic | dopamine D2DR interferons quinpirole NLRP3 inflammasome |
| url | https://www.mdpi.com/2073-4409/11/10/1691 |
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