Distinct proinflammatory host responses to Neisseria gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells
Distinct proinflammatory host responses to Neisseria gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells
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DOI：
10.1128/iai.69.9.5840-5848.2001
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发表时间：
2001-09-01
影响因子：
3.1
通讯作者：
Genco, CA
中科院分区：
文献类型：
--
作者：
Fichorova, RN;Desai, PJ;Genco, CA
在这项研究中，我们利用从形态和功能上不同的正常人宫颈内、外宫颈和阴道永生化的上皮细胞株来表征与女性生殖道下部相关的淋球菌上皮细胞的相互作用。抗生素保护试验和共聚焦显微镜显示，有纤毛但不是无纤毛的淋病奈瑟氏菌F62变异株活跃地入侵这些上皮细胞系。表达绿色荧光蛋白的淋球菌对这些细胞的侵袭以淋球菌与F肌动蛋白共定位为特征，最初在感染30min后检测到。感染纤毛和非纤毛淋球菌4h后，检测到IL-8和IL-6、细胞间黏附分子1(CD54)和非特异性交叉反应抗原(CD66c)表达上调。此外，淋球菌全细胞裂解物对所有三种细胞株的刺激都导致IL-6和IL-8类似的上调，证实细菌摄取对这种反应不是必需的。感染淋球菌后8h，IL-1水平首次升高，提示早期的IL-8和IL-6反应不是通过IL-1信号通路介导的。IL-1的反应仅限于感染纤毛淋球菌的培养物，在宫颈上皮细胞中反应更强烈。淋球菌能在形态和功能上不同的女性生殖道下段刺激不同的促炎宿主反应，这可能直接导致淋球菌引起的疾病的炎症症状和体征。
In this study we utilized immortalized morphologically and functionally distinct epithelial cell lines from normal human endocervix, ectocervix, and vagina to characterize gonococcal epithelial interactions pertinent to the lower female genital tract. Piliated, but not nonpiliated, N. gonorrhoeae strain F62 variants actively invaded these epithelial cell lines, as demonstrated by an antibiotic protection assay and confocal microscopy. Invasion of these cells by green fluorescent protein-expressing gonococci was characterized by colocalization of gonococci with F actin, which were initially detected 30 min postinfection. In all three cell lines, upregulation of interleukin 8 (IL-8) and IL-6, intercellular adhesion molecule 1 (CD54), and the nonspecific cross-reacting antigen (CD66c) were detected 4 h after infection with piliated and nonpiliated gonococci. Furthermore, stimulation of all three cell lines with gonococcal whole-cell lysates resulted in a similar upregulation of IL-6 and IL-8, confirming that bacterial uptake is not essential for this response. Increased levels of IL-1 were first detected 8 h after infection with gonococci, suggesting that the earlier IL-8 and IL-6 responses were not mediated through the IL-1 signaling pathway. The IL-1 response was limited to cultures infected with piliated gonococci and was more vigorous in the endocervical epithelial cells. The ability of gonococci to stimulate distinct proinflammatory host responses in these morphologically and functionally different compartments of the lower female genital tract may contribute directly to the inflammatory signs and symptoms characteristic of disease caused by N. gonorrhoeae.