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细菌性阴道病中生殖器免疫标志物变化与阴道微生物群转变之间的关联

Association between changes in genital immune markers and vaginal microbiome transitions in bacterial vaginosis.

作者信息

Foessleitner Philipp, Cooley Demidkina Briah, El-Arar Wafae, Goldenberg Miles, Murthy Meena, Bergerat Agnes, Bar Ofri, Kwon Douglas S, Mitchell Caroline M

机构信息

Vincent Center for Reproductive Biology, Massachusetts General Hospital, 55 Fruit St, Their 9, Boston, MA, 02114, USA.

Harvard Medical School, Boston, MA, USA.

出版信息

Sci Rep. 2025 Jan 28;15(1):3536. doi: 10.1038/s41598-025-88208-9.

DOI:10.1038/s41598-025-88208-9
PMID:39875510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11775339/
Abstract

Bacterial vaginosis (BV), characterized by an imbalance in the vaginal microbiota, is a prevalent condition among women of reproductive age and a risk factor for human immunodeficiency virus, sexually transmitted infections, and preterm birth. BV is generally considered to induce mucosal inflammation, but the specific pathways and cell types involved are not well characterized. This prospective study aimed to assess associations between microbial changes and mucosal immune responses in BV patients. Therefore, samples from 20 premenopausal women with BV and treated with metronidazole were analyzed. Vaginal swabs, menstrual cup, and endocervical cytobrush samples were collected before treatment, weekly for four weeks, and at 2, 4, and 6 months for Nugent scoring, immune cell populations and cytokine analysis. Of 105 study intervals, 27 (25.7%) showed improvement in Nugent category, 61 (58.1%) remained unchanged, and 17 (16.2%) worsened. Improvement correlated with decreased monocytes (p = 0.005), while worsening was linked to increased monocytes (p < 0.001) and dendritic cells (p = 0.02). B cells (p = 0.02) and IFN-γ-induced chemokines - IP-10 (p = 0.007), MIG (p = 0.049), and ITAC (p = 0.005) - were associated with improvement. In conclusion, although the T-cell-associated chemokines IP-10, ITAC, and MIG were strongly associated with improvements in Nugent category, our findings indicate that antigen-presenting cells, particularly monocytes, show the most dynamic response to shifts in the vaginal microbiota in patients with BV.

摘要

细菌性阴道病(BV)以阴道微生物群失衡为特征,是育龄妇女中的常见病症,也是人类免疫缺陷病毒、性传播感染和早产的危险因素。BV通常被认为会诱发黏膜炎症,但具体涉及的途径和细胞类型尚未得到充分表征。这项前瞻性研究旨在评估BV患者微生物变化与黏膜免疫反应之间的关联。因此,对20名患有BV并接受甲硝唑治疗的绝经前妇女的样本进行了分析。在治疗前、每周一次共四周以及在2、4和6个月时收集阴道拭子、月经杯和宫颈内膜细胞刷样本,用于Nugent评分、免疫细胞群体和细胞因子分析。在105个研究时间段中,27个(25.7%)显示Nugent分类有所改善,61个(58.1%)保持不变,17个(16.2%)恶化。改善与单核细胞减少相关(p = 0.005),而恶化与单核细胞增加(p < 0.001)和树突状细胞增加(p = 0.02)有关。B细胞(p = 0.02)以及IFN-γ诱导的趋化因子——IP-10(p = 0.007)、MIG(p = 0.049)和ITAC(p = 0.005)——与改善相关。总之,尽管与T细胞相关的趋化因子IP-10、ITAC和MIG与Nugent分类的改善密切相关,但我们的研究结果表明,抗原呈递细胞,尤其是单核细胞,对BV患者阴道微生物群的变化表现出最活跃的反应。

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本文引用的文献

1
Vaginal Bacteria and Proinflammatory Host Immune Mediators as Biomarkers of Human Immunodeficiency Virus Acquisition Risk Among African Women.阴道细菌和促炎宿主免疫介质作为非洲女性感染人类免疫缺陷病毒风险的生物标志物
J Infect Dis. 2024 Dec 16;230(6):1444-1455. doi: 10.1093/infdis/jiae406.
2
Metronidazole Treatment Failure and Persistent BV Lead to Increased Frequencies of Activated T- and Dendritic-Cell Subsets.甲硝唑治疗失败与持续性细菌性阴道病导致活化T细胞和树突状细胞亚群频率增加。
Microorganisms. 2023 Oct 27;11(11):2643. doi: 10.3390/microorganisms11112643.
3
IP-10 and MIG are sensitive markers of early virological response to HIV-1 integrase inhibitors.
IP-10 和 MIG 是 HIV-1 整合酶抑制剂早期病毒学应答的敏感标志物。
Front Immunol. 2023 Oct 18;14:1257725. doi: 10.3389/fimmu.2023.1257725. eCollection 2023.
4
Understanding and Preventing Recurring Bacterial Vaginosis: Important Considerations for Clinicians.了解和预防复发性细菌性阴道病:临床医生的重要考量因素
Int J Womens Health. 2023 Aug 9;15:1317-1325. doi: 10.2147/IJWH.S383333. eCollection 2023.
5
Bacterial vaginosis: a review of approaches to treatment and prevention.细菌性阴道病:治疗与预防方法综述
Front Reprod Health. 2023 May 31;5:1100029. doi: 10.3389/frph.2023.1100029. eCollection 2023.
6
Revisited: Species Heterogeneity, Virulence Factors, Mucosal Immune Responses, and Contributions to Bacterial Vaginosis.再探:种间异质性、毒力因子、黏膜免疫应答以及对细菌性阴道病的贡献。
Infect Immun. 2023 May 16;91(5):e0039022. doi: 10.1128/iai.00390-22. Epub 2023 Apr 18.
7
subgroup dominant microbiomes are associated with divergent cervicovaginal immune responses in a longitudinal cohort of Kenyan women.在肯尼亚女性的纵向队列中,亚群优势微生物组与不同的宫颈阴道免疫反应相关。
Front Immunol. 2023 Jan 16;13:974195. doi: 10.3389/fimmu.2022.974195. eCollection 2022.
8
Screening and characterization of vaginal fluid donations for vaginal microbiota transplantation.阴道液供体的筛选和鉴定用于阴道微生物群移植。
Sci Rep. 2022 Oct 26;12(1):17948. doi: 10.1038/s41598-022-22873-y.
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molBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history.molBV 揭示细菌性阴道病的免疫景观,并预测人乳头瘤病毒感染的自然史。
Nat Commun. 2022 Jan 11;13(1):233. doi: 10.1038/s41467-021-27628-3.
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