Advertisement

ResearchIn-Press PreviewImmunologyInfectious disease Open Access | 10.1172/jci.insight.197491

Genital herpes shedding episodes associate with altered spatial organization and activation of mucosal immune cells

Finn MacLean,1 Rachael M. Zemek,1 Adino Tesfahun Tsegaye,2 Jessica B. Graham,1 Jessica L. Swarts,1 Sarah C. Vick,1 Nicole B. Potchen,1 Irene Cruz Talavera,1 Lakshmi Warrier,1 Julien Dubrulle,3 Lena K. Schroeder,3 Anna Elz,4 David Sowerby,4 Ayumi Saito,2 Katherine K. Thomas,2 Matthias Mack,5 Joshua T. Schiffer,1 R. Scott McClelland,2 Keith R. Jerome,1 Bhavna H. Chohan,2 Kenneth Ngure,2 Nelly Rwamba Mugo,2 Evan W. Newell,1 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by MacLean, F. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Zemek, R. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Tsegaye, A. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Graham, J. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Swarts, J. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Vick, S. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Potchen, N. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Cruz Talavera, I. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Warrier, L. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Dubrulle, J. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Schroeder, L. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Elz, A. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Sowerby, D. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Saito, A. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Thomas, K. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Mack, M. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Schiffer, J. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by McClelland, R. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Jerome, K. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Chohan, B. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Ngure, K. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Mugo, N. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Newell, E. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

Find articles by Lingappa, J. in: 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

3Cellular Imaging Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America

4Fred Hutch Innovation Lab, Fred Hutchinson Cancer Center, Seattle, United States of America

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

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

Published November 18, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.197491.
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 November 18, 2025 - Version history
View PDF
Abstract

Herpes Simplex Virus 2 (HSV-2) infection results in variable rates of local viral shedding in anogenital skin. The impact of episodic viral exposures on immune cells in adjacent mucosal tissues, including the genital tract, is unknown. However, any immune responses at this site could impact protective mucosal immunity, tissue homeostasis, and adverse health outcomes. To investigate the impact of HSV-2 on cervicovaginal tract immunity, we applied flow cytometry, immunofluorescent imaging, analysis of soluble immune factors, and spatial transcriptomics to cervicovaginal tissue and blood samples provided by a total of 232 HSV-2-seropositive and seronegative participants, with genital HSV-2 shedding evaluated at the time of biopsy. This unique dataset was used to define and spatially map immune cell subsets and localized gene expression via spatial transcriptomics. HSV-2-seropositivity alone was associated with minimal differences in cervicovaginal and circulating T cell phenotypes. However, the vaginal mucosa during active HSV-2 shedding was associated with alterations in T cell, macrophage, and dendritic cell localization and gene expression consistent with increased immune surveillance, with immune activating and suppressing signals potentially reinforcing mucosal tissue homeostasis.

Supplemental material

View Supplemental Table 1

View Supplemental Table 2

View Supplemental Table 3

View

Version history
  • Version 1 (November 18, 2025): In-Press Preview
Advertisement
Advertisement