Abstract
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.
Keywords: D2DR; NLRP3 inflammasome; dopamine; interferons; quinpirole.
【저자키워드】 interferons, NLRP3 inflammasome, Dopamine, D2DR, quinpirole., 【초록키워드】 SARS-CoV-2, immune response, SARS-COV-2 infection, interferons, antiviral effects, NLRP3 inflammasome, Antiviral effect, Replication, Dopamine, viral replication, mRNA, immune responses, pathway, Inflammasome, mechanisms, receptor, correlation, expression, epithelial, SARS-CoV-2 replication, Calu-3, ISGs, IFNs, ISG, NLRP3, Evidence, administration, Pathways, IFN response, Invasion, host cell, Frame, alteration, downregulation, doses, pro-inflammatory mediators, Calu, cell line, protein levels, lung cells, periphery, while, innate immune pathways, Calu-3 cell line, Alter, recent, non-toxic, robust, quinpirole, affected, significantly, occur, reducing, induce, reduce, turn, downregulating, innate immune pathway, upregulate, 【제목키워드】 SARS-CoV-2, interferons, Dopamine,