Journal
AIDS
Volume 28, Issue 2, Pages 171-180Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000000159
Keywords
breast milk; CD4(+) T cells; exosomes; HIV-1; monocyte-derived dendritic cells; plasma
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Funding
- Swedish Research Council
- Swedish Medical Society
- Stockholm County Council
- IMTAC consortium at Karolinska Institutet
- Milk drop
- Torsten Soderberg's Foundation
- Swedish Cancer Society
- King Gustaf V's 80-years' Foundation
- Magnus Bergvall's Foundation
- Swedish Heart-Lung oundation
- Hesselman's Foundation
- David and Astrid Hagelens' Foundation
- Canadian Institutes of Health Research
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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-1(BaL). To investigate transfer of HIV-1 from MDDCs to CD4(+) T cells, MDDCs preincubated with exosomes and HIV-1(BaL) 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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