Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes
Marloes A. Naarding, Irene S. Ludwig, Fedde Groot, Ben Berkhout, Teunis B.H. Geijtenbeek, Georgios Pollakis, William A. Paxton
Marloes A. Naarding, Irene S. Ludwig, Fedde Groot, Ben Berkhout, Teunis B.H. Geijtenbeek, Georgios Pollakis, William A. Paxton
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Research Article AIDS/HIV

Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes

Abstract

DC-specific ICAM3-grabbing non-integrin (DC-SIGN), which is expressed on DCs, can interact with a variety of pathogens such as HIV-1, hepatitis C, Ebola, cytomegalovirus, Dengue virus, Mycobacterium, Leishmania, and Candida albicans. We demonstrate that human milk can inhibit the DC-SIGN–mediated transfer of HIV-1 to CD4+ T lymphocytes as well as viral transfer by both immature and mature DCs. The inhibitory factor directly interacted with DC-SIGN and prevented the HIV-1 gp120 envelope protein from binding to the receptor. The human milk proteins lactoferrin, α-lactalbumin, lysozyme, β-casein, and secretory leukocyte protease inhibitor did not bind DC-SIGN or demonstrate inhibition of viral transfer. The inhibitory effect could be fully alleviated with an Ab recognizing the Lewis X (LeX) sugar epitope, commonly found in human milk. LeX in polymeric form or conjugated to protein could mimic the inhibitory activity, whereas free LeX sugar epitopes could not. We reveal that a LeX motif present in human milk can bind to DC-SIGN and thereby prevent the capture and subsequent transfer of HIV-1 to CD4+ T lymphocytes. The presence of such a DC-SIGN–binding molecule in human milk may both influence antigenic presentation and interfere with pathogen transfer in breastfed infants.

Authors

Marloes A. Naarding, Irene S. Ludwig, Fedde Groot, Ben Berkhout, Teunis B.H. Geijtenbeek, Georgios Pollakis, William A. Paxton

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Direct infection of CD4+ T lymphocytes in the presence of human milk. (A...
Direct infection of CD4+ T lymphocytes in the presence of human milk. (A) PBS or several dilutions of human milk from an uninfected mother were spiked with LAI (X4) and added to CD4-enriched T lymphocytes. After a 2-hour incubation, the CD4+ T lymphocytes were washed, and fresh medium was added. (B) LAI (X4) was incubated with a 1:2 dilution of human milk or PBS for 2 hours, after which several dilutions were made and added to CD4+ T lymphocytes. For both experiments the CA-p24 concentration was determined on day 7. *P < 0.05 compared with the PBS control.