Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota

Mucosal Immunol. 2017 Sep;10(5):1310-1319. doi: 10.1038/mi.2016.129. Epub 2017 Jan 25.

Abstract

Cervical human papillomavirus (HPV) infection may increase HIV risk. Since other genital infections enhance HIV susceptibility by inducing inflammation, we assessed the impact of HPV infection and clearance on genital immunology and the cervico-vaginal microbiome. Genital samples were collected from 65 women for HPV testing, immune studies and microbiota assessment; repeat HPV testing was performed after 6 months. All participants were HIV-uninfected and free of bacterial STIs. Cytobrush-derived T cell and dendritic cell subsets were assessed by multiparameter flow cytometry. Undiluted cervico-vaginal secretions were used to determine cytokine levels by multiplex ELISA, and to assess bacterial community composition and structure by 16S rRNA gene sequence analysis. Neither HPV infection nor clearance were associated with broad differences in cervical T cell subsets or cytokines, although HPV clearance was associated with increased Langerhans cells and HPV infection with elevated IP-10 and MIG. Individuals with HPV more frequently had a high diversity cervico-vaginal microbiome (community state type IV) and were less likely to have an L. gasseri predominant microbiome. In summary, HPV infection and/or subsequent clearance was not associated with inflammation or altered cervical T cell subsets, but associations with increased Langerhans cells and the composition of the vaginal microbiome warrant further exploration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL9 / metabolism
  • Cytokines / metabolism
  • Female
  • Herpes Genitalis / immunology
  • Herpes Genitalis / microbiology*
  • Herpesvirus 2, Human / physiology*
  • Humans
  • Langerhans Cells / immunology*
  • Microbiota / genetics*
  • Middle Aged
  • RNA, Ribosomal, 16S / analysis*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / virology
  • Vagina / immunology*
  • Vagina / microbiology
  • Viral Load

Substances

  • CXCL10 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Cytokines
  • RNA, Ribosomal, 16S