Influence of Lactic Acid on Endogenous and Viral RNA-Induced Immune Mediator Production by Vaginal Epithelial Cells

Mossop, Hannah; Linhares, Iara M.; Bongiovanni, Ann Marie; Ledger, William J.

doi:10.1097/aog.0b013e31822da9e9

Cited by 41 publications

(40 citation statements)

References 30 publications

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“…In contrast, lactic acid-producing bacteria produce both the d - and l -lactic acid isomers (2). We and others have also presented evidence that l -lactic acid, in addition to its role in influencing vaginal acidity, has specific immune properties, such as stimulation of the interleukin 23 (IL-23)/IL-17 T lymphocyte pathway (14, 15), induction of proinflammatory cytokines by vaginal epithelial cells in the presence of a synthetic viral RNA (16), induction of tumor angiogenesis (17), lymphocyte activation (18), and inhibition of bacterial growth (19, 20). However, the role that d -lactic acid plays in the vaginal ecosystem has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Influence of Vaginal Bacteria andd- andl-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections

Witkin

Mendes‐Soares

Linhares

et al. 2013

mBio

Self Cite

289

235

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We evaluated levels of vaginal extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP-8) in vaginal secretions in relation to the composition of vaginal bacterial communities and d- and l-lactic acid levels. The composition of vaginal bacterial communities in 46 women was determined by pyrosequencing the V1 to V3 region of 16S rRNA genes. Lactobacilli were dominant in 71.3% of the women, followed by Gardnerella (17.4%), Streptococcus (8.7%), and Enterococcus (2.2%). Of the lactobacillus-dominated communities, 51.5% were dominated by Lactobacillus crispatus, 36.4% by Lactobacillus iners, and 6.1% each by Lactobacillus gasseri and Lactobacillus jensenii. Concentrations of l-lactic acid were slightly higher in lactobacillus-dominated vaginal samples, but most differences were not statistically significant. d-Lactic acid levels were higher in samples containing L. crispatus than in those with L. iners (P < 0.0001) or Gardnerella (P = 0.0002). The relative proportion of d-lactic acid in vaginal communities dominated by species of lactobacilli was in concordance with the proportions found in axenic cultures of the various species grown in vitro. Levels of l-lactic acid (P < 0.0001) and the ratio of l-lactic acid to d-lactic acid (P = 0.0060), but not concentrations of d-lactic acid, were also correlated with EMMPRIN concentrations. Moreover, vaginal concentrations of EMMPRIN and MMP-8 levels were highly correlated (P < 0.0001). Taken together, the data suggest the relative proportion of l- to d-lactic acid isomers in the vagina may influence the extent of local EMMPRIN production and subsequent induction of MMP-8. The expression of these proteins may help determine the ability of bacteria to transverse the cervix and initiate upper genital tract infections.

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Section: Introductionmentioning

confidence: 99%

Influence of Vaginal Bacteria andd- andl-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections

Witkin

Mendes‐Soares

Linhares

et al. 2013

mBio

Self Cite

289

235

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“…It has also been found that LA in its acidic form increases the release of antiviral mediators from vaginal epithelial cells (27). This cytokine response is specific for LA and occurs solely at an acidic pH.…”

Section: Discussionmentioning

confidence: 92%

Theaflavin-3,3′-Digallate and Lactic Acid Combinations Reduce Herpes Simplex Virus Infectivity

Isaacs

2013

Antimicrob Agents Chemother

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The present study examined the efficacy of using multiple mechanisms as part of a topical microbicide to inactivate herpes simplex virus (HSV) by combining theaflavin-3,3=-digallate (TF-3) and lactic acid (LA) over the pH range of 4.0 to 5.7 to mimic conditions in the female reproductive tract. Six clinical isolates of HSV-2 and two clinical isolates of HSV-1 were almost completely inactivated when TF-3 (100 M) was present with LA over the pH range of 4.5 to 5.7, whereas four additional HSV-1 clinical isolates required TF-3 concentrations of 250 to 500 M for comparable virus titer reduction. LA (1%) alone at pH 4.0 reduced the titers of laboratory and clinical isolates of HSV-1 and HSV-2 by >5 log 10 , but most LA-dependent antiviral activity was lost at a pH of >4.5. When HSV-1 and HSV-2 were incubated at pH 4.0 without LA virus titers were not reduced. At pH 4.0, HSV-1 and HSV-2 titers were reduced 5 log 10 in 20 min by LA alone. TF-3 reduced HSV-2 titers by 5 log 10 in 20 to 30 min at pH 4.5, whereas HSV-1 required 60 min for comparable inactivation. Mixtures of TF-3 and LA stored at 37°C for 1 month at pH 4.0 to 5.7 maintained antiviral activity. Semen, but not cervical vaginal fluid, decreased LA-dependent antiviral activity at pH 4.0, but adding TF-3 to the mixture reduced HSV titers by 4 to 5 log 10 . These results indicate that a combination microbicide containing TF-3 and LA could reduce HSV transmission.

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“…Undoubtedly there exists a complex interplay between the vaginal microbiota and host immune response, both locally and systemically, as well its metabolic milieu. For example, lactic acid enhances the release of IL-1β and IL-8 from vaginal epithelial cells, suggesting a synergistic relationship between inflammatory activation in the host and microbial composition, which is likely dependent on both intrinsic (genetic) and extrinsic (environmental) factors58. Moreover, although vaginal epithelial cells produce only L-lactic acid isomer59, lactic acid-producing bacteria including Lactobacillus spp.…”

Section: Discussionmentioning

confidence: 99%

The vaginal microbiome during pregnancy and the postpartum period in a European population

MacIntyre

Chandiramani

Lee

et al. 2015

Sci Rep

437

429

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The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were sampled longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha-diversity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii-dominated microbiome characterised by low alpha-diversity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes.

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Influence of Lactic Acid on Endogenous and Viral RNA-Induced Immune Mediator Production by Vaginal Epithelial Cells

Abstract: Lactic acid enhances the release of selective mediators from vaginal epithelial cells and stimulates antiviral immune responses.

Cited by 41 publications

References 30 publications

Influence of Vaginal Bacteria andd- andl-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections

Influence of Vaginal Bacteria andd- andl-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections

Theaflavin-3,3′-Digallate and Lactic Acid Combinations Reduce Herpes Simplex Virus Infectivity

The vaginal microbiome during pregnancy and the postpartum period in a European population

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