Naarding Marloes A, Ludwig Irene S, Groot Fedde, Berkhout Ben, Geijtenbeek Teunis B H, Pollakis Georgios, Paxton William A
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Clin Invest. 2005 Nov;115(11):3256-64. doi: 10.1172/JCI25105. Epub 2005 Oct 20.
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, alpha-lactalbumin, lysozyme, beta-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.
树突状细胞特异性细胞间黏附分子3抓取非整合素（DC-SIGN）表达于树突状细胞（DC），可与多种病原体相互作用，如HIV-1、丙型肝炎病毒、埃博拉病毒、巨细胞病毒、登革热病毒、分枝杆菌、利什曼原虫和白色念珠菌。我们证明，人乳可抑制DC-SIGN介导的HIV-1向CD4+T淋巴细胞的转移以及未成熟和成熟DC的病毒转移。抑制因子直接与DC-SIGN相互作用，阻止HIV-1 gp120包膜蛋白与受体结合。人乳中的乳铁蛋白、α-乳白蛋白、溶菌酶、β-酪蛋白和分泌型白细胞蛋白酶抑制剂不与DC-SIGN结合，也不显示对病毒转移的抑制作用。用识别常见于人乳中的Lewis X（LeX）糖表位的抗体可完全消除抑制作用。聚合形式或与蛋白质偶联的LeX可模拟抑制活性，而游离的LeX糖表位则不能。我们发现人乳中存在的LeX基序可与DC-SIGN结合，从而防止HIV-1捕获并随后转移至CD4+T淋巴细胞。人乳中这种与DC-SIGN结合的分子的存在可能既影响抗原呈递，又干扰母乳喂养婴儿中病原体的转移。
