Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses.
Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses.
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阴道加德纳菌通过微生物特异性免疫应答改变宫颈阴道上皮细胞功能。
DOI：
10.1186/s40168-022-01317-9
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发表时间：
2022-08-04
期刊：
影响因子：
15.5
通讯作者：
中科院分区：
文献类型：
--
作者：
宫颈阴道 (CV) 微生物群与怀孕和非怀孕个体的阴道健康和疾病高度相关。 CV 腔内过多的阴道加德纳菌 (G. vaginalis) 通常与不良生殖后果相关，包括细菌性阴道病 (BV)、性传播疾病和早产，而乳酸杆菌属的存在则可能导致不良生殖后果。通常与生殖健康有关。虽然宿主-微生物相互作用被认为有助于心血管健康和疾病，但这些相互作用调节心血管上皮功能的机制仍然很大程度上未知。使用体外共培养模型，我们评估了卷曲乳杆菌 (L. Criphatus) 和阴道 G. vaginalis 对 CV 上皮屏障、可能导致屏障完整性下降的免疫介质以及调节免疫反应的免疫信号通路的影响。 G. vaginalis，但不是 L. Criphatus，以上皮细胞特异性的方式显着增加上皮细胞死亡并降低上皮屏障完整性。阴道 G. vaginalis 介导的上皮免疫反应（包括 NF-κB 激活和促炎细胞因子释放）部分是通过 TLR2 依赖性信号通路启动的。此外，对人类CV液中细胞因子免疫谱的研究表明，加德纳菌属细胞因子具有独特的聚集性。丰度和出生结果。这项研究的结果显示了微生物对CV上皮功能的特异性影响。阴道加盖菌（而非卷曲乳杆菌）通过细胞死亡和免疫介导机制改变上皮屏障功能，表明宿主上皮细胞对细菌相关信号做出反应，导致上皮功能改变，最终导致心血管疾病。此外，与加德纳菌属相关的独特免疫特征。或出生结果提供了进一步的证据，表明宿主-微生物相互作用可能对调节生殖结果的生物机制做出重大贡献。视频摘要 在线版本包含可在 10.1186/s40168-022-01317-9 获取的补充材料。
The cervicovaginal (CV) microbiome is highly associated with vaginal health and disease in both pregnant and nonpregnant individuals. An overabundance of Gardnerella vaginalis (G. vaginalis) in the CV space is commonly associated with adverse reproductive outcomes including bacterial vaginosis (BV), sexually transmitted diseases, and preterm birth, while the presence of Lactobacillus spp. is often associated with reproductive health. While host-microbial interactions are hypothesized to contribute to CV health and disease, the mechanisms by which these interactions regulate CV epithelial function remain largely unknown. Using an in vitro co-culture model, we assessed the effects of Lactobacillus crispatus (L. crispatus) and G. vaginalis on the CV epithelial barrier, the immune mediators that could be contributing to decreased barrier integrity and the immune signaling pathways regulating the immune response. G. vaginalis, but not L. crispatus, significantly increased epithelial cell death and decreased epithelial barrier integrity in an epithelial cell-specific manner. A G. vaginalis-mediated epithelial immune response including NF-κB activation and proinflammatory cytokine release was initiated partially through TLR2-dependent signaling pathways. Additionally, investigation of the cytokine immune profile in human CV fluid showed distinctive clustering of cytokines by Gardnerella spp. abundance and birth outcome. The results of this study show microbe-specific effects on CV epithelial function. Altered epithelial barrier function through cell death and immune-mediated mechanisms by G. vaginalis, but not L. crispatus, indicates that host epithelial cells respond to bacteria-associated signals, resulting in altered epithelial function and ultimately CV disease. Additionally, distinct immune signatures associated with Gardnerella spp. or birth outcome provide further evidence that host-microbial interactions may contribute significantly to the biological mechanisms regulating reproductive outcomes. Video Abstract The online version contains supplementary material available at 10.1186/s40168-022-01317-9.
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影响因子：
2.3
作者：
Dude, Carolynn M.;Saylany, Anissa;Anton, Lauren
通讯作者：
Anton, Lauren
影响因子：
5.2
作者：
Anton L;Sierra LJ;DeVine A;Barila G;Heiser L;Brown AG;Elovitz MA
通讯作者：
Elovitz MA
DOI：
10.1073/pnas.1502875112
发表时间：
2015-09-01
影响因子：
11.1
作者：
DiGiulio, Daniel B.;Callahan, Benjamin J.;Relman, David A.
通讯作者：
Relman, David A.
影响因子：
9.8
作者：
Elovitz, Michal A.;Anton, Lauren;Brown, Amy G.
通讯作者：
Brown, Amy G.
影响因子：
3.2
作者：
Ahmed, Azad;Earl, Josh;Ehrlich, Garth D.
通讯作者：
Ehrlich, Garth D.