MacLean Finn, Tsegaye Adino Tesfahun, Graham Jessica B, Swarts Jessica L, Vick Sarah C, Potchen Nicole, Talavera Irene Cruz, Warrier Lakshmi, Dubrulle Julien, Schroeder Lena K, Saito Ayumi, Thomas Katherine K, Mack Matthias, Sabo Michelle C, Chohan Bhavna H, Ngure Kenneth, Mugo Nelly, Lingappa Jairam R, Lund Jennifer M
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, USA.
Department of Global Health, University of Washington, Seattle, USA.
bioRxiv. 2025 Jan 14:2024.07.03.601916. doi: 10.1101/2024.07.03.601916.
Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent among reproductive-age females worldwide. Adverse health outcomes associated with BV include an increased risk of sexually-acquired HIV, yet the immunological mechanisms underlying this association are not well understood. To investigate BV-driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and PBMC samples. High-parameter flow cytometry revealed an increased frequency of cervical conventional CD4 T cells (Tconv) expressing CCR5. However, we found no difference in number of CD3CD4CCR5 cells in the CX or VT of BV+ vs BV- individuals, suggesting that BV-driven increased HIV susceptibility may not be solely attributed to increased CVT HIV target cell abundance. Flow cytometry also revealed that individuals with BV have an increased frequency of dysfunctional CX and VT CD39 Tconv and CX tissue-resident CD69CD103 Tconv, reported to be implicated in HIV acquisition risk and replication. Many soluble immune factor differences in the CVT further support that BV elicits diverse and complex CVT immune alterations. Our comprehensive analysis expands on potential immunological mechanisms that may underlie the adverse health outcomes associated with BV including increased HIV susceptibility.
细菌性阴道病（BV）是一种阴道微生物群失调症，在全球育龄女性中普遍存在。与BV相关的不良健康后果包括性传播HIV风险增加，然而这种关联背后的免疫机制尚未完全了解。为了研究BV驱动的宫颈阴道 tract（CVT）和循环T细胞表型变化，有或没有BV的参与者提供了阴道 tract（VT）和宫颈外口（CX）组织活检样本以及外周血单核细胞（PBMC）样本。高参数流式细胞术显示，表达CCR5的宫颈常规CD4 T细胞（Tconv）频率增加。然而，我们发现BV+个体与BV-个体的CX或VT中CD3CD4CCR5细胞数量没有差异，这表明BV驱动的HIV易感性增加可能不仅仅归因于CVT HIV靶细胞丰度增加。流式细胞术还显示，患有BV的个体功能失调的CX和VT CD39 Tconv以及CX组织驻留CD69CD103 Tconv频率增加，据报道这些细胞与HIV感染风险和复制有关。CVT中许多可溶性免疫因子差异进一步支持BV引发了多样且复杂的CVT免疫改变。我们的综合分析扩展了可能是与BV相关的不良健康后果（包括HIV易感性增加）基础的潜在免疫机制。
