Saeland Eirikur, de Jong Marein A W P, Nabatov Alexey A, Kalay Hakan, Geijtenbeek Teunis B H, van Kooyk Yvette
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Mol Immunol. 2009 Jul;46(11-12):2309-16. doi: 10.1016/j.molimm.2009.03.025. Epub 2009 Apr 29.
Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in mucosal areas that allow efficient transmission of the virus to T cells. Here, we demonstrate that the epithelial mucin MUC1, abundant in milk, efficiently bound to DC-SIGN on DC. The O-linked glycans within the mucin domain contained Lewis X structures, that were specifically recognized by the receptor. Interestingly, MUC1 prevented DC-SIGN-mediated transmission of HIV-1 from DCs to CD4+ T cells. We hypothesize that repetitive units of Lewis X, within the mucin domain, play an important role in inhibiting transmission of HIV-1 from mother to child.
人类免疫缺陷病毒1型(HIV-1)的母婴传播经常通过母乳喂养发生。HIV-1靶向黏膜区域中表达DC-SIGN的树突状细胞(DC),从而使病毒能够有效地传播至T细胞。在此,我们证明乳汁中丰富的上皮粘蛋白MUC1能有效地结合DC上的DC-SIGN。粘蛋白结构域内的O-连接聚糖含有Lewis X结构,该结构可被受体特异性识别。有趣的是,MUC1可阻止DC-SIGN介导的HIV-1从DC向CD4+ T细胞的传播。我们推测,粘蛋白结构域内Lewis X的重复单元在抑制HIV-1母婴传播中发挥重要作用。