Bacterial Vaginosis-driven Changes in Cervicovaginal Immunity That Expand the Immunological Hypothesis for Increased HIV Susceptibility

Overview

Journal bioRxiv

Date 2024 Jul 15

PMID 39005354

Authors

Finn MacLean

Adino Tesfahun Tsegaye

Jessica B Graham

Jessica L Swarts

Sarah C Vick

Nicole Potchen

Irene Cruz Talavera

Lakshmi Warrier

Julien Dubrulle

Lena K Schroeder

Corinne Mar

Ayumi Saito

Katherine K Thomas

Matthias Mack

Michelle C Sabo

Bhavna H Chohan

Kenneth Ngure

Nelly Mugo

Jairam R Lingappa

Jennifer M Lund

Affiliations

Soon will be listed here.

Abstract

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.

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