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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The major milk proteins are not responsible for the inhibitory effect of...
The major milk proteins are not responsible for the inhibitory effect of human milk. (A and B) Raji-DC-SIGN cells or iDCs were incubated with the major milk proteins before addition of fluorescent gp120–coated beads; control cells were incubated with buffer. To determine the specificity of the observed binding, the cells were incubated with AZN-D1, EGTA, and mannan before addition of the gp120 beads. The asterisks represent P < 0.01 compared with noninhibitory control. (C) The major milk proteins were coated on ELISA plates, and DC-SIGN-Fc binding was measured. To determine the specificity of the observed binding, the DC-SIGN-Fc was preincubated with AZN-D1 and EGTA. *P < 0.01 compared with both the AZN-D1 and EGTA control. In all experiments the major proteins were diluted to a 1:20 dilution of their physiological concentration in human milk.