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


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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.

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