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The Villain Team-Up or how Trichomonas vaginalis and bacterial vaginosis alter innate immunity in concert
  1. Raina N Fichorova1,
  2. Olivia R Buck1,
  3. Hidemi S Yamamoto1,
  4. Titilayo Fashemi1,
  5. Hassan Y Dawood1,
  6. Bisiayo Fashemi1,
  7. Gary R Hayes2,
  8. David H Beach3,
  9. Yuko Takagi4,
  10. Mary L Delaney5,
  11. Max L Nibert4,
  12. Bibhuti N Singh2,6,
  13. Andrew B Onderdonk5
  1. 1Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  2. 2Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, New York, USA
  3. 3Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, New York, USA
  4. 4Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
  5. 5Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  6. 6Department of Obstetrics and Gynecology, SUNY Medical University, Syracuse, New York, USA
  1. Correspondence to Dr Raina Fichorova, Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave RF468, Boston, MA 02115, USA; rfichorova{at}rics.bwh.harvard.edu

Abstract

Objectives Complex interactions of vaginal microorganisms with the genital tract epithelium shape mucosal innate immunity, which holds the key to sexual and reproductive health. Bacterial vaginosis (BV), a microbiome-disturbance syndrome prevalent in reproductive-age women, occurs commonly in concert with trichomoniasis, and both are associated with increased risk of adverse reproductive outcomes and viral infections, largely attributable to inflammation. To investigate the causative relationships among inflammation, BV and trichomoniasis, we established a model of human cervicovaginal epithelial cells colonised by vaginal Lactobacillus isolates, dominant in healthy women, and common BV species (Atopobium vaginae, Gardnerella vaginalis and Prevotella bivia).

Methods Colonised epithelia were infected with Trichomonas vaginalis (TV) or exposed to purified TV virulence factors (membrane lipophosphoglycan (LPG), its ceramide-phosphoinositol-glycan core (CPI-GC) or the endosymbiont Trichomonas vaginalis virus (TVV)), followed by assessment of bacterial colony-forming units, the mucosal anti-inflammatory microbicide secretory leucocyte protease inhibitor (SLPI), and chemokines that drive pro-inflammatory, antigen-presenting and T cells.

Results TV reduced colonisation by Lactobacillus but not by BV species, which were found inside epithelial cells. TV increased interleukin (IL)-8 and suppressed SLPI, likely via LPG/CPI-GC, and upregulated IL-8 and RANTES, likely via TVV as suggested by use of purified pathogenic determinants. BV species A vaginae and G vaginalis induced IL-8 and RANTES, and also amplified the pro-inflammatory responses to both LPG/CPI-GC and TVV, whereas P bivia suppressed the TV/TVV-induced chemokines.

Conclusions These molecular host–parasite–endosymbiont–bacteria interactions explain epidemiological associations and suggest a revised paradigm for restoring vaginal immunity and preventing BV/TV-attributable inflammatory sequelae in women.

  • TRICHOMONAS
  • VAGINAL MICROBIOLOGY
  • IMMUNOLOGY
  • BACTERIAL VAGINOSIS
  • WOMEN

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