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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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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DC-SIGN–dependent transfer of HIV-1 to CD4+ T lymphocytes is inhibited i...
DC-SIGN–dependent transfer of HIV-1 to CD4+ T lymphocytes is inhibited in the presence of human milk. (A) A 1:2 dilution of human milk of an uninfected mother or PBS was spiked with primary isolates NSI-18 (R5) or SI-19 (X4) before addition to Raji-DC-SIGN cells. After an incubation of 30 minutes or 2 hours, the cells were washed, and activated CD4+ T lymphocytes were added. Viral replication was measured on days 7, 9, 12, and 14 after infection by determining CA-p24 values using a standard ELISA. The bars represent maximum and minimum CA-p24 values. (B) PBS or serial dilutions of human milk were spiked with JR-CSF (R5) or LAI (X4) before addition of Raji-DC-SIGN cells; after an incubation of 2 hours, the cells were washed with PBS, and stimulated CD4+ T lymphocytes were added. At day 7, CA-p24 concentrations were determined by standard ELISA. Percent inhibition was determined in reference to the CA-p24 concentration of the corresponding spiked PBS control.