Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age
Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age
复制标题
DOI：
10.1371/journal.pone.0224359
复制
发表时间：
2020-01-08
期刊：
影响因子：
3.7
通讯作者：
Doncel, Gustavo F.
中科院分区：
文献类型：
--
作者：
Fichorova, Raina N.;Morrison, Charles S.;Doncel, Gustavo F.
性传播感染（STI）和阴道生态失调（存在异常Nugent评分或念珠菌病的居民微生物群失调）与粘膜炎症和HIV-1感染，癌症和不良生殖结果的风险有关。迄今为止，尚未在大量育龄妇女中研究异常宫颈先天免疫与微生物紊乱临床发作之间的时间关系。我们研究了来自934名乌干达和津巴布韦妇女的纵向队列数据，这些妇女提供了3，274次艾滋病毒阴性就诊，她们有完整的实验室，临床和人口统计学数据。其中，207名妇女后来感染了艾滋病毒，584名妇女间歇性地被诊断为C。trachomatis（CT）、N.淋病（NG）、生殖器疱疹（HSV-2）、T.阴道炎（TV）、念珠菌病和异常中等（4 - 6）或高（7 - 10）Nugent评分，即细菌性阴道病（BV）。通过广义线性和混合效应模型分析宫颈拭子中的免疫生物标志物浓度，调整了研究中心、年龄、激素避孕药使用（HC）、妊娠、母乳喂养、生殖器实践、无保护性行为和重叠感染。高似然比（1.5 - 4.9）表示宫颈免疫生物标志物的值可以预测下次访视时异常Nugent评分和念珠菌病的发生。当控制协变量时，较高水平的β-防御素-2是BV、CT和HSV-2的前因，较低的抗炎比率IL-1RA：IL-1 β-与中间Nugent评分和念珠菌，较低水平的丝氨酸蛋白酶抑制剂SLPI-与念珠菌，较低水平的粘附分子ICAM-1-与TV，以及较低水平的氧化应激缓解剂和内皮活化标记物VEGF-与NG。当控制所有其他协变量时，生态失调和感染发作后先天免疫的变化取决于HC的使用。总之，迫在眉睫的女性生殖道生态失调或感染可以预测的先天免疫的不同模式。未来的研究应该描述这种预先存在的先天免疫状态的生物和非生物决定因素。
Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of beta-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1 beta-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.