The role of Toll-like receptor on sexual transmission of HIV

虽然许多研究表明，在存在其他性传播疾病的情况下，感染艾滋病毒的风险更高，但导致艾滋病毒感染增加的生物机制尚不清楚。由于朗格汉斯细胞（LC）被怀疑是性暴露后的初始HIV靶点，我们研究了微生物成分是否通过激活TLR和NOD模式识别受体来增强LC中的HIV感染。我们发现，TLR 1/2和TLR 2/6激动剂显着增强艾滋病毒的易感性和复制在未成熟的单核细胞衍生的LC。当LC与其他相关细菌组分以及与全革兰氏阳性细菌一起孵育时，观察到相同的感染增强效应。在人类皮肤中的常驻LC中，TLR 2激动剂也显著增加了HIV易感性。我们发现LCs的TLR 2活化导致APOBEC 3G的显著下调，APOBEC 3G是HIV的细胞限制因子。鉴于这些数据，我们假设，革兰氏阳性细菌产物对TLR 2的连接可能是伴随细菌性传播疾病感染而发生的HIV性传播增强的基础。

Although numerous studies have shown a higher risk of acquiring HIV infection in the presence of other sexually transmitted diseases, the biologic mechanisms responsible for enhanced HIV acquisition are unclear. Because Langerhans cells (LCs) are suspected to be the initial HIV targets after sexual exposure, we studied whether microbial components augment HIV infection in LCs by activating TLR and NOD pattern recognition receptors. We found that TLR1/2 and TLR2/6 agonists dramatically enhanced both HIV susceptibility and replication in immature monocyte-derived LCs. The same infection-enhancing effects were observed when LCs were incubated with other related bacterial components as well as with whole Gram+ bacteria. In resident LCs in human skin, TLR2 agonists also significantly increased HIV susceptibility. We found that TLR2 activation of LCs, resulted in a significant down-regulation of APOBEC3G, which is a cellular restriction factor for HIV. Given these data, we hypothesize that ligation of TLR2 by Gram+ bacterial products may underlie enhanced sexual transmission of HIV that occurs with concomitant bacterial sexually transmitted disease infections.