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Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines
  1. Michelle C Sabo1,
  2. Dara A Lehman2,3,
  3. Bingjie Wang4,
  4. Barbra A Richardson3,5,6,
  5. Sujatha Srinivasan2,
  6. Lusi Osborn7,
  7. Daniel Matemo7,
  8. John Kinuthia3,8,
  9. Tina L Fiedler2,
  10. Matthew M Munch2,
  11. Alison L Drake3,
  12. David N Fredricks2,
  13. Julie Overbaugh4,
  14. Grace John-Stewart1,3,5,9,
  15. R. Scott McClelland1,3,5,8,
  16. Susan M Graham1,3,5
  1. 1 Department of Internal Medicine, University of Washington, Seattle, Washington, USA
  2. 2 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  3. 3 Department of Global Health, University of Washington, Seattle, Washington, USA
  4. 4 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  5. 5 Department of Epidemiology, University of Washington, Seattle, Washington, USA
  6. 6 Department of Biostatistics, University of Washington, Seattle, Washington, United States
  7. 7 Department of Research and Programs, Kenyatta National Hospital, Nairobi, Kenya
  8. 8 Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
  9. 9 Seattle Children's Hospital, Seattle, Washington, USA
  1. Correspondence to Dr Michelle C Sabo, Internal Medicine, Seattle, WA 98105, USA; sabo{at}


Objectives Recent studies have identified vaginal bacterial taxa associated with increased HIV risk. A possible mechanism to explain these results is that individual taxa differentially promote cervicovaginal inflammation. This study aimed to explore relationships between concentrations of bacteria previously linked to HIV acquisition and vaginal concentrations of proinflammatory cytokines and chemokines.

Methods In this cross-sectional analysis, concentrations of 17 bacterial taxa and four proinflammatory cytokines (interleukin (IL)-1β, IL-6, IL-10 and tumour necrosis factor alpha (TNFα)) and two proinflammatory chemokines (IL-8 and interferon gamma-induced protein 10) were measured in vaginal swabs collected from 80 HIV-uninfected women. Cytokine and chemokine concentrations were compared between women with bacterial concentrations above or below the lower limit of detection as determined by quantitative PCR for each taxon. Principal component analysis was used to create a summary score for closely correlated bacteria, and linear regression analysis was used to evaluate associations between this score and increasing concentrations of TNFα and IL-1β.

Results Detection of Dialister micraerophilus (p=0.01), Eggerthella sp type 1 (p=0.05) or Mycoplasma hominis (p=0.03) was associated with higher TNFα concentrations, and detection of D. micraerophilus (p<0.01), Eggerthella sp type 1 (p=0.04), M. hominis (p=0.02) or Parvimonas sp type 2 (p=0.05) was associated with significantly higher IL-1β concentrations. Seven bacterial taxa (D. micraerophilus, Eggerthella sp type 1, Gemella asaccharolytica, Sneathia sp, Megasphaera sp, M. hominis and Parvimonas sp type 2) were found to be highly correlated by principal component analysis (eigenvalue 5.24, explaining 74.92% of variability). Linear regression analysis demonstrated associations between this principal component and concentrations of TNFα (β=0.55, 95% CI 0.01 to 1.08; p=0.048) and IL-1β (β=0.96, 95% CI 0.19 to 1.74; p=0.016).

Conclusions This study provides evidence that several highly correlated vaginal bacterial taxa may influence vaginal cytokine and chemokine concentrations. These results suggest a mechanism where the presence of specific bacterial taxa could influence HIV susceptibility by increasing vaginal inflammation.

  • vaginal microbiology
  • sexual health
  • Trichomonas
  • immunology
  • HIV women
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  • Handling editor Jo-Ann Passmore

  • Contributors ALD, JK, DM, BAR, JO, RSM and GJS were involved in design of the parent studies, and SMG conceived the present analysis. JK, ALD, DM, LO and GJS performed data collection. MCS, DAL, BW, BAR, JO and SMG participated in data analysis. DNF and SS were involved in design and implementation of quantitative PCR procedures. TLF and MMM performed qPCR data collection and analysis. BW and DAL generated cytokine data. JO, GJS, RSM and DNF acquired funding for this study. BAR provided statistical guidance. MCS and SMG wrote the initial draft of the manuscript. All authors contributed to the final draft of the manuscript and approved the final draft for submission.

  • Funding This study was supported by the National Institute of Child Health and Human Development of the National Institutes of Health (NIH P01-HD64915). Data and sample collection in the Mombasa Cohort were supported through the National Institute of Allergy and Infectious Diseases of the NIH (NIH R37 AI38518). The Mombasa research site receives infrastructure support from the University of Washington Center for AIDS Research (NIH P30-AI27757). RSM receives funding for mentoring through NIH K24 HD88229. ALD receives support from K01 AI116298. MCS is supported by the T32 Host Defense Training grant (NIH 5T32AI007044-43 PI, van Voorhis) as an infectious disease fellow. SMG was supported by the Robert W Anderson Endowed Professorship in Medicine.

  • Competing interests RSM receives research funding, paid to the University of Washington, from Hologic. TLF has a patent, Molecular Diagnosis of Bacterial Vaginosis, licensed to Becton Dickinson. SS, MMM, DAL and TLF report grants from the NIH during the conduct of the study. All other authors have nothing to disclose.

  • Patient consent for publication Not required.

  • Ethics approval Kenyatta National Hospital (KNH) Ethics Review Committee (ERC), application number: P197/04/2012–University of Washington (UW) Human Subjects Committee, IRB number STUDY00000615-KNH ERC, application number: P114/04/2010, renewed in 2018–UW Human Subjects Committee, IRB number 38472.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data relevant to the study are included in the article or uploaded as supplementary information.

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