Departmentsof Medicine (Gastroenterology), University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
J Leukoc Biol. 2010 Apr;87(4):663-70. doi: 10.1189/jlb.0909605. Epub 2009 Dec 9.
To dissect the early events in the transmission of HIV-1 from mother to child, we investigated whether DCs participate in HIV-1 entry into human small intestinal mucosa. We isolated human MNLs from jejunal lamina propria and identified a subpopulation of CD11c(+)HLA-DR(+) MNLs that expressed DC-SIGN, CD83, CD86, CD206, and CCR7, indicating a DC phenotype. Jejunal DCs also expressed the HIV-1 receptor CD4 and coreceptors CCR5 and CXCR4 and in suspension rapidly took up cell-free HIV-1. HIV-1 inoculated onto the apical surface of explanted jejunum was transported by lamina propria DCs through the mucosa and transmitted in trans to blood and intestinal lymphocytes. These findings indicate that in addition to intestinal epithelial cells, which we showed previously transcytose infectious HIV-1 to indicator cells, intestinal DCs play an important role in transporting HIV-1 through the intestinal mucosa and the subsequent transmission to T cells.
为了剖析 HIV-1 从母亲传播给儿童的早期事件,我们研究了树突状细胞(DCs)是否参与了 HIV-1 进入人体小肠黏膜的过程。我们从空肠固有层中分离出人类 MNLs,并鉴定出一群表达 DC-SIGN、CD83、CD86、CD206 和 CCR7 的 CD11c(+)HLA-DR(+)MNLs,表明其具有 DC 表型。空肠 DCs 还表达 HIV-1 受体 CD4 和辅助受体 CCR5 和 CXCR4,并且在悬浮状态下能够迅速摄取无细胞 HIV-1。将 HIV-1 接种到离体空肠的顶端表面后,固有层 DCs 通过黏膜将其转运,并通过trans 向血液和肠道淋巴细胞传播。这些发现表明,除了我们之前证明的能够将感染性 HIV-1 转导给指示细胞的肠上皮细胞外,肠道 DCs 在将 HIV-1 通过肠黏膜转运以及随后向 T 细胞传播方面发挥着重要作用。