The role of DC-SIGN in HIV-1 transmission through dendritic cells
Objective To identify the role of DC-SIGN in HIV-1 transmission by peripheral dendritic cells (DC).Methods Immature DC(iDC) and mature DC(mDC) stimulated with M-or T-tropic HIV-1 primary isolates were cocultured with activated CD4~+ T cells.The level of HIV-1 p24 antigen in ceculture supernatant was detected by quantitative ELISA method at day 4,7,10,14 to evaluate the role of DC in dissemination of HIV-1.iDC and mDC were preincubated with anti-DC-SIGN monoclonal antibody(McAb) and/or anti-ICAM-3 McAb before HIV-1 stimula- tion to find the effects of the two antibodies on DC transmission of HIV-1.Results The level of p24 antigen in cocul- ture supernatant of iDC stimulated by M-tropic HIV-1 and mDC stimulated by M- and T-tropic HIV-1 increased and was significantly higher than that of the controls (P=0.001).The upregulated level of p24 antigen in coculture super- natant of T-tropic HIV-1-stimulated iDC was not observed in controls.The level of p24 antigen decreased in supernat ants of iDC primed with M-tropic HIV-1 and mDC primed with M- or T-tropic HIV-1 after preincubation with anti-DC- SIGN McAb,but not with anti-ICAM-3 McAb.Conclusion iDC may play a role in the transmission of HIV-1 with M-tropic,but not T-tropic HIV-1 transmission,mDC may transmit both M-tropic and T-tropic HIV-1 to CD4~+ T cells. The inhibition of HIV-1 transmission by anti-DC-SIGN McAb showed that DC-SIGN may facilitate HIV-1 dissemination from DC to T cells.