The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention.
The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention.
复制标题
DOI：
10.1038/mi.2016.97
复制
发表时间：
2017-07
影响因子：
8
通讯作者：
Amara RR
中科院分区：
文献类型：
--
作者：
Kelley CF;Kraft CS;de Man TJ;Duphare C;Lee HW;Yang J;Easley KA;Tharp GK;Mulligan MJ;Sullivan PS;Bosinger SE;Amara RR
男男性行为者（MSM）中的大多数艾滋病毒传播，占2014年美国新感染病例的67%，通过暴露于直肠粘膜发生。然而，目前还不清楚如何无套接受性肛交（CRAI）的行为可能会改变粘膜免疫环境的HIV阴性男男性接触者。在这里，我们进行了一个全面的表征直肠粘膜免疫环境的表型和生产的促炎细胞因子的CD4和CD8 T细胞，全球转录组学分析，和组成的微生物群在HIV阴性MSM。我们的研究结果表明，与从未进行过肛交的男性相比，从事CRAI的MSM的直肠粘膜具有独特的表型，其特征在于更高水平的Th17细胞，更大的CD8+ T细胞增殖和促炎细胞因子的产生，与粘膜损伤相关的分子特征和可能由先天免疫细胞介导的修复，以及富含Prevotellaceae家族的微生物群。这些数据提供了一个高分辨率模型的免疫学，分子和微生物的扰动引起的CRAI，将有直接的效用，在了解直肠艾滋病毒传播的男男性接触者，并将加强设计未来的生物医学预防干预措施，包括候选的艾滋病毒疫苗。
Most HIV transmissions among men who have sex with men (MSM), the group that accounted for 67% of new US infections in 2014, occur via exposure to the rectal mucosa. However, it is unclear how the act of condomless receptive anal intercourse (CRAI) may alter the mucosal immune environment in HIV negative MSM. Here, we performed a comprehensive characterization of the rectal mucosal immune environment for the phenotype and production of pro-inflammatory cytokines by CD4 and CD8 T cells, global transcriptomic analyses, and the composition of microbiota in HIV negative MSM. Our results show that compared to men who had never engaged in anal intercourse, the rectal mucosa of MSM engaging in CRAI has a distinct phenotype characterized by higher levels of Th17 cells, greater CD8+ T cell proliferation and production of pro-inflammatory cytokines, molecular signatures associated with mucosal injury and repair likely mediated by innate immune cells, and a microbiota enriched for the Prevotellaceae family. These data provide a high-resolution model of the immunological, molecular, and microbiological perturbations induced by CRAI, will have direct utility in understanding rectal HIV transmission among MSM, and will enhance the design of future biomedical prevention interventions, including candidate HIV vaccines.