Exosomes from breast milk inhibit HIV-1 infection of dendritic cells and subsequent viral transfer to CD4+ T cells

Abstract

OBJECTIVE: To investigate whether exosomes derived from human breast milk or plasma confer protection against HIV-1 infection of monocyte-derived dendritic cells (MDDCs) and subsequent viral transfer to CD4 T cells. DESIGN: MDDCs were generated and milk and plasma-derived exosomes were isolated from healthy donors. To determine the capacity of exosomes to inhibit HIV-1 infection, MDDCs were preincubated with exosomes before exposure to HIV-1BaL. To investigate transfer of HIV-1 from MDDCs to CD4 T cells, MDDCs preincubated with exosomes and HIV-1BaL were cocultured with allogeneic CD4 T cells. To explore receptors used by MDDCs for binding of exosomes, blocking experiments were performed. METHODS: Productive HIV-1 infection was analysed in MDDCs and CD4 T cells by determining p24 expression by flow cytometry. Confocal microscopy and flow cytometry was used to investigate uptake of fluorescently labelled exosomes by MDDCs. RESULTS: Milk exosomes, but not plasma exosomes, bind MDDCs via DC-SIGN inhibiting HIV-1 infection of MDDCs and subsequent viral transfer to CD4 T cells. CONCLUSION: We propose that milk exosomes act as a novel protective factor against vertical transmission of HIV-1 by competing with HIV-1 for binding to DC-SIGN on MDDCs.