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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Incubation of human milk (1:20) with LeX IgM Ab relieves the inhibitory ...
Incubation of human milk (1:20) with LeX IgM Ab relieves the inhibitory properties of human milk on DC-SIGN–mediated transfer of HIV-1 to CD4+ T lymphocytes. (A) A 1:200 dilution of human milk was incubated alone, with IgM control Ab (4,000 ng/ml), or with serial dilutions of LeX IgM Ab (4,000 to 32.7 ng/ml) before addition of Raji-DC-SIGN cells. LAI was added, and following a short incubation, the cells were washed, and activated CD4+ T lymphocytes were added, with CA-p24 values determined at day 7. *P < 0.05 compared with the Raji-DC-SIGN control. (B) Human milk (1:200) was coated and preincubated with anti-LeX IgM Ab (4,000 ng/ml) or an IgM control Ab (4,000 ng/ml) before addition of DC-SIGN-Fc to determine binding. DC-SIGN-Fc was preincubated with AZN-D1and EGTA to determine the specificity of the observed binding. **P < 0.01 compared with the human milk binding without Ab present.