Within 1 h, HIV-1 uses viral synapses to enter efficiently the inner, but not outer, foreskin mucosa and engages Langerhans-T cell conjugates
Within 1 h, HIV-1 uses viral synapses to enter efficiently the inner, but not outer, foreskin mucosa and engages Langerhans-T cell conjugates
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DOI：
10.1038/mi.2010.32
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发表时间：
2010-09-01
影响因子：
8
通讯作者：
Bomsel, M.
中科院分区：
文献类型：
--
作者：
Ganor, Y.;Zhou, Z.;Bomsel, M.
虽然包皮环切术减少了60%的男性获得人类免疫缺陷病毒1型（HIV-1），HIV-1在包皮传播的最初机制仍然难以捉摸。我们已经建立了两种新的和互补的模型，即，离体包皮外植体和体外重建免疫活性包皮的人成人包皮上皮。在这些模型中，有效的HIV-1传播发生后1小时的极化暴露的内部，但不是外部，包皮高度感染HIV-1的单核细胞，但不是无细胞病毒。HIV-1感染的细胞与顶端包皮角质形成细胞形成病毒突触，导致HIV-1的极化出芽，其被内包皮中的朗格汉斯细胞（LC）迅速内化。反过来，LC向表皮-真皮界面迁移，与T细胞形成缀合物，从而转移HIV-1。精浆与宫颈阴道分泌物混合可抑制HIV-1易位。这组结果在细胞水平上合理化包皮环切术对男性获得HIV-1的明显保护效果。
Although circumcision reduces male acquisition of human immunodeficiency virus type-1 (HIV-1) by 60%, the initial mechanisms of HIV-1 transmission at the foreskin remain elusive. We have established two novel and complementary models of the human adult foreskin epithelium, namely, ex vivo foreskin explants and in vitro reconstructed immunocompetent foreskins. In these models, efficient HIV-1 transmission occurs after 1 h 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 migrate toward the epidermis-dermis interface to form conjugates with T cells, thereby transferring HIV-1. Seminal plasma mixed with cervicovaginal secretions inhibits HIV-1 translocation. This set of results rationalizes at the cellular level the apparent protective outcome of circumcision against HIV-1 acquisition by men.