Advertisement

Clinical Research and Public HealthIn-Press PreviewAIDS/HIVImmunologyInfectious disease Open Access | 10.1172/JCI184609

Bacterial vaginosis associates with dysfunctional T cells and altered soluble immune factors in the cervicovaginal tract

Finn MacLean,1 Adino Tesfahun Tsegaye,2 Jessica B. Graham,3 Jessica L. Swarts,3 Sarah C. Vick,1 Nicole B. Potchen,1 Irene Cruz Talavera,1 Lakshmi Warrier,1 Julien Dubrulle,4 Lena K. Schroeder,4 Ayumi Saito,2 Corinne Mar,2 Katherine K. Thomas,2 Matthias Mack,5 Michelle C. Sabo,6 Bhavna H. Chohan,2 Kenneth Ngure,2 Nelly Rwamba Mugo,2 Jairam R. Lingappa,2 and Jennifer M. Lund1

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by MacLean, F. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Tsegaye, A. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Graham, J. in: JCI | PubMed | Google Scholar |

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Swarts, J. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Vick, S. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Potchen, N. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Cruz Talavera, I. in: JCI | PubMed | Google Scholar |

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Warrier, L. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Dubrulle, J. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Schroeder, L. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Saito, A. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Mar, C. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Thomas, K. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Mack, M. in: JCI | PubMed | Google Scholar |

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Sabo, M. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Chohan, B. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Ngure, K. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Mugo, N. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Lingappa, J. in: JCI | PubMed | Google Scholar

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States of America

2Department of Global Health, University of Washington, Seattle, United States of America

3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

4Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Internal Medicine-Nephrology, University Hospital Regensburg, Regensburg, Germany

6Department of Medicine, University of Washington, Seattle, United States of America

Find articles by Lund, J. in: JCI | PubMed | Google Scholar |

Published March 25, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI184609.
Copyright © 2025, MacLean et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published March 25, 2025 - Version history
View PDF
Abstract

Background: 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. Methods: To investigate BV-driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, Kinga Study participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and PBMC samples. Results: 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 CD3+CD4+CCR5+ cells in the CX or VT of BV+ versus 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 CD69+CD103+ 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. Conclusion: Our comprehensive analysis expands on potential immunological mechanisms that may underlie the adverse health outcomes associated with BV including increased HIV susceptibility.

Supplemental material

View

View Supplemental Table 1

View Supplemental Table 2

View Supplemental Table 3

Version history
  • Version 1 (March 25, 2025): In-Press Preview
Advertisement
Advertisement