Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes
Marloes A. Naarding, … , Georgios Pollakis, William A. Paxton
Marloes A. Naarding, … , Georgios Pollakis, William A. Paxton
Published November 1, 2005
Citation Information: J Clin Invest. 2005;115(11):3256-3264. https://doi.org/10.1172/JCI25105.
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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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Human milk inhibits the transfer of HIV-1 by iDCs and mDCs. (A) Both iDC...
Human milk inhibits the transfer of HIV-1 by iDCs and mDCs. (A) Both iDCs and mDCs from the same donor were incubated with several dilutions of human milk for 30 minutes before addition of LAI (X4). After 2 hours the cells were washed, and LuSIV cells were added; after 24 hours the LuSIV cells were washed, and the luciferase activity was determined as described in Methods. The asterisks represent statistical differences in infections (P < 0.05). (B) After an incubation of iDCs with human milk or PBS, the cells were washed and LAI was added. After an incubation of 2 hours, the cells were washed again, and captured CA-p24 levels were monitored via ELISA. **P < 0.05 compared with the corresponding control value for both experiments. (C) iDCs were incubated with TSM or human milk (1:2) before the binding of AZN-D1, AZN-D2, and anti-stalk 4 DC-SIGN–specific Abs were determined. The filled histograms represent the isotype control; the black lines represent the Ab binding without human milk preincubation; and the dotted lines represent the Ab binding after the cells were incubated with human milk.