Vaginal dysbiosis associated-bacteria Megasphaera elsdenii and Prevotella timonensis induce immune activation via dendritic cells

Teijlingen, Nienke H. van; Helgers, Leanne C.; Willems, Esther; Hamme, John L. van; Ribeiro, Carla M. S.; Strijbis, Karin; Geijtenbeek, Teunis B. H.

doi:10.1016/j.jri.2020.103085

Cited by 51 publications

(33 citation statements)

References 44 publications

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“…To our knowledge, the pro-inflammatory host response to cervical infection with M. micronuciformis has not been previously examined in vitro, though another species under the Megasphaera genus (Megasphaera elsdenii) has been investigated 54 . In this study, dendritic cells elevated secretion of IL-1β, IL-6, IL-8, IL-12p40, and TNF-α in response to infection with M. elsdenii 54 . Additionally, M. micronuciformis was associated with genital inflammation as measured from cervicovaginal fluid in a cohort of South African adolescent females 55 .…”

Section: Discussionmentioning

confidence: 99%

Veillonellaceae family members uniquely alter the cervical metabolic microenvironment in a human three-dimensional epithelial model

Salliss

Maarsingh

Garza

et al. 2021

npj Biofilms Microbiomes

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Bacterial vaginosis (BV) is a gynecologic disorder characterized by a shift in cervicovaginal microbiota from Lactobacillus spp. dominance to a polymicrobial biofilm composed of diverse anaerobes. We utilized a well-characterized human three-dimensional cervical epithelial cell model in conjunction with untargeted metabolomics and immunoproteomics analyses to determine the immunometabolic contribution of three members of the Veillonellaceae family: Veillonella atypica, Veillonella montpellierensis and Megasphaera micronuciformis at this site. We found that Veillonella spp. infections induced significant elevation of polyamines. M. micronuciformis infections significantly increased soluble inflammatory mediators, induced moderate levels of cell cytotoxicity, and accumulation of cell membrane lipids relative to Veillonella spp. Notably, both V. atypica and V. montpellierensis infections resulted in consumption of lactate, a key metabolite linked to gynecologic and reproductive health. Collectively our approach and data provide unique insights into the specific contributions of Veillonellaceae members to the pathogenesis of BV and women’s health.

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Section: Discussionmentioning

confidence: 99%

Veillonellaceae family members uniquely alter the cervical metabolic microenvironment in a human three-dimensional epithelial model

Salliss

Maarsingh

Garza

et al. 2021

npj Biofilms Microbiomes

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“…BV-related bacteria have been shown to induce immune activation through dendritic cell maturation and to increase levels of proinflammatory cytokines, resulting in mucosal inflammation of the genital tract. 43,44 Higher levels of cervical interleukin (IL)-1b, IL-6, and IL-8 cytokines have been reported in women with infertility and BV. 45 Restoration of normal vaginal microbiota with use of a probiotic vaginal tablet containing lactobacilli has been shown to reduce levels of proinflammatory cytokines, 46 The species of Lactobacillus used in the vaginal tablet were L brevis, L salivarius subsp.…”

Section: Expert Reviewmentioning

confidence: 99%

Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease

Ravel

Moreno

Simón

2021

American Journal of Obstetrics and Gynecology

182

112

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Bacterial vaginosis, pelvic inflammatory disease, and endometritis are infections of the genital tract that can lead to many adverse health outcomes, including infertility. Bacterial vaginosis is characterized by a lower prevalence of lactobacilli and a higher prevalence of anaerobic bacteria, including Gardnerella vaginalis, Megasphaera spp., and Atopobium vaginae. Endometritis and pelvic inflammatory disease are caused by the ascension of pathogenic bacteria to the uterus, although the mechanisms by which they do so are unclear. Bacterial vaginosis, chronic endometritis, and pelvic inflammatory disease have been linked to infertility in retrospective and prospective trials. Similarly, the causes of bacterial vaginosis and endometritis-related infertility are likely multifactorial and stem from inflammation, immune targeting of sperm antigens, the presence of bacterial toxins, and increased risk of sexually transmitted infections. Diagnosis and treatment of bacterial vaginosis, chronic endometritis, and pelvic inflammatory disease before attempting conception may be important components of preconceptional care for symptomatic women to improve outcomes of natural and assisted reproduction.

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“…A more in-depth investigation of the relationship between vaginal bacteria, immune response and persistent infection and, in detail, how some vaginal bacteria can affect the adaptive immune response was performed by van Teijlingen et al [ 47 ]. The authors studied the effect of two species often reported in vaginal dysbiosis CST-IV, Megasphaera eldsenii and Prevotella timonensis, on the activation of dendritic cells (DCs) and compared their effects with those induced by L. crispatus .…”

Section: Discussionmentioning

confidence: 99%

Vaginal Lactobacilli and Vaginal Dysbiosis-Associated Bacteria Differently Affect Cervical Epithelial and Immune Homeostasis and Anti-Viral Defenses

Nicolò

Tanturli

Mattiuz

et al. 2021

IJMS

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Persistent infection with High Risk-Human Papilloma Viruses (HR-HPVs) is a primary cause of cervical cancer worldwide. Vaginal-dysbiosis-associated bacteria were correlated with the persistence of HR-HPVs infection and with increased cancer risk. We obtained strains of the most represented bacterial species in vaginal microbiota and evaluated their effects on the survival of cervical epithelial cells and immune homeostasis. The contribution of each species to supporting the antiviral response was also studied. Epithelial cell viability was affected by culture supernatants of most vaginal-dysbiosis bacteria, whereas Lactobacillus gasseri or Lactobacillus jensenii resulted in the best stimulus to induce interferon-γ (IFN-γ) production by human mononuclear cells from peripheral blood (PBMCs). Although vaginal-dysbiosis-associated bacteria induced the IFN-γ production, they were also optimal stimuli to interleukin-17 (IL-17) production. A positive correlation between IL-17 and IFN-γ secretion was observed in cultures of PBMCs with all vaginal-dysbiosis-associated bacteria suggesting that the adaptive immune response induced by these strains is not dominated by TH1 differentiation with reduced availability of IFN-γ, cytokine most effective in supporting virus clearance. Based on these results, we suggest that a vaginal microbiota dominated by lactobacilli, especially by L. gasseri or L. jensenii, may be able to assist immune cells with clearing HPV infection, bypasses the viral escape and restores immune homeostasis.

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Vaginal dysbiosis associated-bacteria Megasphaera elsdenii and Prevotella timonensis induce immune activation via dendritic cells

Cited by 51 publications

References 44 publications

Veillonellaceae family members uniquely alter the cervical metabolic microenvironment in a human three-dimensional epithelial model

Veillonellaceae family members uniquely alter the cervical metabolic microenvironment in a human three-dimensional epithelial model

Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease

Vaginal Lactobacilli and Vaginal Dysbiosis-Associated Bacteria Differently Affect Cervical Epithelial and Immune Homeostasis and Anti-Viral Defenses

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