Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events.
Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events.
复制标题
DOI：
10.1371/journal.pone.0146663
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Quayle AJ
中科院分区：
文献类型：
--
作者：
Buckner LR;Amedee AM;Albritton HL;Kozlowski PA;Lacour N;McGowin CL;Schust DJ;Quayle AJ
沙眼衣原体引起主要无症状，但通常是炎症性生殖器感染，这与艾滋病毒感染风险增加有关。宫颈内上皮细胞为这种专性细胞内细菌提供了主要的生态位，宫颈内也是艾滋病毒传播可能发生的组织。然而，CT感染增强该部位HIV易感性的机制尚不清楚。利用在细胞培养插入物上生长的A2EN永生化宫颈上皮细胞系，我们评估了ct感染的上皮细胞在促进HIV传播事件中的直接作用。我们确定，CT感染显著增强了细胞相关（而非无细胞）HIVBaL病毒（一种嗜ccr5的病毒株）穿过宫颈内膜上皮屏障的根尖向基底侧迁移。我们还证实，来自ct感染的A2EN细胞的基底外侧上清液显著增强了外周单核细胞和CCR5+ T细胞系中的HIV复制。这些结果表明，宫颈上皮细胞的CT感染可以促进HIV穿过粘膜屏障，并随后在潜在的靶细胞中感染或复制。我们的研究提供了一种机制，通过这种常见的性传播感染可能促进创始病毒种群的建立和维持宫颈内局部HIV库。艾滋病毒/性传播感染合并感染模型的开发也为进一步探索其他性传播感染在增加艾滋病毒感染中的作用提供了工具。
Chlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also a tissue in which HIV transmission can occur. The mechanism by which CT infection enhances HIV susceptibility at this site, however, is not well understood. Utilizing the A2EN immortalized endocervical epithelial cell line grown on cell culture inserts, we evaluated the direct role that CT-infected epithelial cells play in facilitating HIV transmission events. We determined that CT infection significantly enhanced the apical-to-basolateral migration of cell-associated, but not cell-free, HIVBaL, a CCR5-tropic strain of virus, across the endocervical epithelial barrier. We also established that basolateral supernatants from CT-infected A2EN cells significantly enhanced HIV replication in peripheral mononuclear cells and a CCR5+ T cell line. These results suggest that CT infection of endocervical epithelial cells could facilitate both HIV crossing the mucosal barrier and subsequent infection or replication in underlying target cells. Our studies provide a mechanism by which this common STI could potentially promote the establishment of founder virus populations and the maintenance of local HIV reservoirs in the endocervix. Development of an HIV/STI co-infection model also provides a tool to further explore the role of other sexually transmitted infections in enhancing HIV acquisition.