期刊
CELLS
卷 11, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/cells11101691
关键词
dopamine; D2DR; interferons; quinpirole; NLRP3 inflammasome
类别
资金
- Bando Regione Lombardia DG Welfare [RL_DGWEL20MBIAS_01]
- CARIPLO-EXTRABANDO E PROGETTI TERRITORIALI [CAR_EXT20MBIAS_01]
Recent evidence shows that the SARS-CoV-2 virus inhibits immune responses through dopamine-related mechanisms. In this study, the role of dopamine in SARS-CoV-2 replication was investigated in human lung cells, revealing that dopamine can reduce viral replication and affect the expression of D1 and D2 dopamine receptors. Additionally, dopamine can upregulate the expression of ISGs and Type-I interferons, while downregulating pro-inflammatory mediators. These findings highlight the correlation between dopamine pathways and the Type-I interferon response, which may be disrupted by SARS-CoV-2 for invasion and replication in host cells.
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.
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