Calcitriol decreases HIV-1 transfer in vitro from monocyte-derived dendritic cells to CD4 + T cells, and downregulates the expression of DC-SIGN and SIGLEC-1.
Natalia AlvarezSandra M GonzalezJuan C HernandezMaria T RugelesWbeimar Aguilar-JimenezPublished in: PloS one (2022)
Dendritic cells (DCs) promote HIV-1 transmission by acting as Trojan horses, capturing viral particles, facilitating the infection of CD4+ T-cells. Vitamin D (VitD) has shown to decrease T cell activation, reducing susceptibility to HIV-1 infection of CD4+ T-cells in vitro; however, if VitD decreases viral transfer from DCs to CD4+ T-cells is unknown. In this study, we co-cultured HIV-1-pulsed immature and LPS mature monocytes-derived DCs (iDCs and LmDCs, respectively), differentiated in presence or absence of calcitriol (VitD active form), with PHA-activated autologous CD4+ T-cells from 16 healthy donors. In co-cultures of iDCs and LmDCs treated with calcitriol, there was a significant decrease in frequency of infected CD4+ T-cells, evaluated by flow cytometry. However, p24 levels evaluated by ELISA were not significantly reduced in culture supernatants. Moreover, calcitriol-treated iDCs exhibited decreased expression of genes involved in HIV-1 transfer compared to the control. Both, calcitriol-treated iDCs and LmDCs exhibit a similar gene expression profile, probably related to a transcriptional balance achieved after long treatment with calcitriol. Since calcitriol-differentiated DCs express on their surface a lower amount of DC-SIGN and SIGLEC-1 molecules, widely associated with HIV-1 transfer, suggesting that this mechanism contributes to a lower transfer of viral particles by the DCs.
Keyphrases
- dendritic cells
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- human immunodeficiency virus
- hiv aids
- hepatitis c virus
- men who have sex with men
- poor prognosis
- immune response
- sars cov
- regulatory t cells
- gene expression
- genome wide
- endothelial cells
- bone marrow
- oxidative stress
- platelet rich plasma
- mesenchymal stem cells
- stem cells
- peripheral blood
- cell therapy
- monoclonal antibody
- newly diagnosed
- nk cells
- smoking cessation
- replacement therapy