Mycoplasma genitalium promotes epithelial crossing and peripheral blood mononuclear cell infection by HIV-1.
Mycoplasma genitalium promotes epithelial crossing and peripheral blood mononuclear cell infection by HIV-1.
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DOI：
10.1016/j.ijid.2013.11.022
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发表时间：
2014-06
期刊：
影响因子：
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通讯作者：
Dhandayuthapani S
中科院分区：
文献类型：
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作者：
Das K;De la Garza G;Siwak EB;Scofield VL;Dhandayuthapani S
据报道，HIV感染者合并生殖支原体感染可增加女性泌尿生殖道HIV的脱落。为了更好地理解这种关系，我们研究了M。生殖器对艾滋病毒的传播和复制使用体外模型。采用Transwell共培养系统评估HIV-1穿过宫颈内细胞屏障的情况。用免疫细胞化学和共聚焦显微镜观察nectin-1分子在M. End 1/E6 E7宫颈内细胞系的生殖器感染上皮细胞，在插入物威尔斯孔中生长为单层。外周血单个核细胞（PBMC）在底部威尔斯孔中培养以评估M.生殖器，通过半渗透性培养膜，对随后的HIV感染易感靶细胞。用粘附阳性的M.生殖器G37菌株（野生型）显著提高了HIV穿过上皮细胞屏障的通过，相对于HIV穿过用粘附阴性M感染的宫颈内细胞的转移。生殖器JB 1菌株。免疫组化染色显示M.生殖器G37感染的上皮细胞揭示了连接调节蛋白nectin-1的加帽和内化，与细胞单层中降低的跨上皮电阻（TER）相关。当PBMC在含有M.生殖器-G37感染的上皮细胞单层，我们观察到显着增强的感染性和复制的HIV后加入到文化。M.生殖器感染影响培养的粘膜上皮单层两侧的事件：（1）通过感染上皮细胞并降低屏障本身的完整性，以及（2）通过激活其下方的HIV靶细胞，从而促进HIV感染和子代病毒产生。
Mycoplasma genitalium co-infection in HIV-infected individuals has been reported to increase the shedding of HIV in the urogenital region of females. To better understand this relationship, we investigated the influence of M. genitalium on the transmission and replication of HIV using an in vitro model. The Transwell co-culture system was employed to assess the crossing of an endocervical cell barrier by HIV-1. Immunocytochemistry and confocal microscopy were used to assess the distribution of the nectin-1 molecule on M. genitalium-infected epithelial cells of the End1/E6E7 endocervical cell line, grown as monolayers in the insert wells. Peripheral blood mononuclear cells (PBMC) were cultured in the bottom wells to assess the effects of M. genitalium, passing through the semipermeable culturing membrane, on subsequent HIV infection of susceptible target cells. Infection of the endocervical cells with the adhesion-positive M. genitalium G37 strain (wild-type) significantly elevated the passage of HIV across the epithelial cell barrier relative to HIV transfer across endocervical cells infected with the adhesion-negative M. genitalium JB1 strain. Immunostaining of the M. genitalium-G37-infected epithelial cells disclosed capping and internalization of the junctional regulatory protein nectin-1, in association with reduced transepithelial resistance (TER) in the cell monolayer. When PBMC were cultured beneath insert wells containing M. genitalium-G37-infected epithelial cell monolayers, we observed significantly enhanced infectivity and replication of HIV added afterward to the cultures. M. genitalium influences events on both sides of a cultured mucosal epithelial monolayer: (1) by infecting the epithelial cells and reducing the integrity of the barrier itself, and (2) by activating HIV target cells below it, thereby promoting HIV infection and progeny virus production.