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. 2020 Feb;96(1):3-9.
doi: 10.1136/sextrans-2018-053949. Epub 2019 Jun 13.

Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines

Michelle C Sabo  1 , Dara A Lehman  2   3 , Bingjie Wang  4 , Barbra A Richardson  3   5   6 , Sujatha Srinivasan  2 , Lusi Osborn  7 , Daniel Matemo  7 , John Kinuthia  3   8 , Tina L Fiedler  2 , Matthew M Munch  2 , Alison L Drake  3 , David N Fredricks  2 , Julie Overbaugh  4 , Grace John-Stewart  9   3   5   10 , R Scott McClelland  9   3   5   8 , Susan M Graham  9   3   5
Affiliations

Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines

Michelle C Sabo et al. Sex Transm Infect. 2020 Feb.

Abstract

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.

Keywords: HIV women; Trichomonas; immunology; sexual health; vaginal microbiology.

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Conflict of interest statement

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.

Figures

Figure 1:
Figure 1:. Box plots of log2 transformed cytokine level by detection of bacterial taxa.
The log2 of cytokine concentrations when bacterial taxa were below (dark bars) or above (white bars) the lower limit of detection. P-values were calculated using the Wilcoxon rank-sum test. The lower limits of detection for each cytokine are as follows: IL-1β, 0.048 pcg/mL; IL-6, 0.164 pcg/mL; IL-8, 0.090 pcg/mL; IL-10, 0.033 pcg/mL; TNFα 0.118 pcg/mL; IP-10, 0.109 pcg/mL.
See this image and copyright information in PMC

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