Mucosal Entry of HIV-1 and Mucosal Immunity, Cell Biology and Host Pathogen Interactions Department, Cochin Institute, Université Paris Descartes, CNRS-UMR 8104, 22 rue Méchain, Paris, France.
Am J Reprod Immunol. 2011 Mar;65(3):284-91. doi: 10.1111/j.1600-0897.2010.00933.x. Epub 2010 Nov 28.
HIV-1 is mainly a sexually transmitted infection, and epithelial surfaces covering genital mucosa are the primary site of HIV-1 transmission. Although male circumcision was reported to reduce male acquisition of HIV-1 by 60%, the initial mechanisms of HIV-1 transmission in the male genitals remain elusive. We established two novel models of the adult human foreskin epithelium that allowed for polarized infection via the mucosal pole with either HIV-1-infected cells that are present in all secretions vectorizing HIV-1 or cell-free HIV-1. Efficient HIV-1 transmission occurs following 1 hr of polarized exposure of the inner, but not outer, foreskin to mononuclear cells highly infected with HIV-1, but not to cell-free virus. HIV-1-infected cells form viral synapses with apical foreskin keratinocytes, leading to polarized budding of HIV-1, which is rapidly internalized by Langerhans cells (LCs) in the inner foreskin. In turn, LCs form conjugates with T-cells, thereby transferring HIV-1. Seminal plasma from HIV-negative men mixed with cervico-vaginal secretions from HIV-positive women, which mimics the in-vivo mixture of these genital fluids during woman-to-man HIV-1 sexual transmission, decreases HIV-1 infection at the foreskin. Our results rationalize at the cellular level the apparent protective outcome of circumcision against HIV-1 acquisition by men.
HIV-1 主要通过性传播感染，而覆盖生殖器黏膜的上皮表面是 HIV-1 传播的主要部位。虽然有报道称男性包皮环切术可使男性感染 HIV-1 的风险降低 60%，但男性生殖器中 HIV-1 传播的初始机制仍不清楚。我们建立了两种新的成人包皮上皮模型，允许通过黏膜极以感染细胞或游离 HIV-1 对上皮进行极化感染，这些感染细胞存在于所有传播 HIV-1 的分泌物中。在将高度感染 HIV-1 的单核细胞极化暴露于内包皮 1 小时后，会发生有效的 HIV-1 传播，但不会发生游离病毒的传播。感染 HIV-1 的细胞与包皮角质形成细胞的顶端形成病毒突触，导致 HIV-1 极性出芽，这些病毒很快被内包皮中的朗格汉斯细胞（LCs）内化。反过来，LCs 与 T 细胞形成共轭，从而转移 HIV-1。来自 HIV-阴性男性的精液与来自 HIV-阳性女性的宫颈阴道分泌物混合，模拟了女性向男性 HIV-1 性传播过程中这些生殖液的体内混合，降低了包皮的 HIV-1 感染。我们的研究结果从细胞水平上解释了男性包皮环切术对预防 HIV-1 感染的明显保护作用。
