Microbiome, sex hormones, and immune responses in the reproductive tract: Challenges for vaccine development against sexually transmitted infections

Brotman, Rebecca M.; Ravel, Jacques; Bavoil, Patrik M.; Gravitt, Patti E.; Ghanem, Khalil G.

doi:10.1016/j.vaccine.2013.10.010

Cited by 88 publications

(95 citation statements)

References 119 publications

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“…Therefore, we found that CYP1A1 and Catechol-o-methyltransferase (COMT) work in a metabolic sequence and their interaction could lead to an alternative pathway of oestrogen metabolism with production of 16-OH-estrone that is more proliferative and less apoptotic [42,43]. The role of oestrogen and the association of CSTs favourable for balance vaginal milieu, was previously debated [44].…”

Section: Catechoestrogens and Cytochrome P450 (Cyp1a1)mentioning

confidence: 99%

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Matos¹,

Silva²,

Medeiros³

et al. 2018

Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control

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Current knowledge point to persistence of risk factors for the development of cervical intraepithelial neoplasia. The infection with a high-risk oncogenic Human Papillomavirus (HPV) subtypes, most commonly 16 and 18, is a necessary, although not sufficient, condition for development of invasive cervical cancer (ICC) and its precancerous precursor, cervical intra-epithelial neoplasia (CIN). It has been suggested that CIN disease severity and the diversity of vaginal microbiota are associated and this may determine viral persistence and disease behaviour. Our work focuses on the genetic variability associated to the modulation of genotoxicity induced by vaginal microbiota diversity. Relatively little is known about the mechanisms associated with clearance or persistence of HPV infection, therefore we hypothesized that may be under the influence of the genetic background.

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Section: Catechoestrogens and Cytochrome P450 (Cyp1a1)mentioning

confidence: 99%

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Matos¹,

Silva²,

Medeiros³

et al. 2018

Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control

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“…Protection from infection is also achieved through the integrity of a mucus layer that protects the epithelial barrier, and the presence of diverse microbial communities, collectively termed the microbiome (1). These protective mechanisms are critically important in preventing acquisition of sexually transmitted infections (STIs) (2, 3). In particular, mucosal immune integrity is important in preventing new human immunodeficiency virus (HIV) infections and HIV exposure at mucosal surfaces, such as the rectum or the vaginal tract, constitutes the major route for HIV transmission.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function

Manuzak

Hensley-McBain

Zevin

et al. 2016

The Journal of Immunology

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Given the critical role of mucosal surfaces in susceptibility to infection, it is imperative that effective mucosal responses are induced when developing efficacious vaccines and prevention strategies for infection. Modulating the microbiota in the gastrointestinal (GI) tract through the use of probiotics (PBio) is a safe and well-tolerated approach to enhance mucosal and overall health. We assessed the longitudinal impact of daily treatment with the VSL#3 probiotic on cellular and humoral immunity and inflammation in healthy macaques. PBio therapy resulted in significantly increased frequencies of B cells expressing IgA in the colon and lymph node (LN), likely due to significantly increased LN T follicular helper cell (Tfh) frequencies and LN follicles. Increased frequencies of IL-23+ antigen presenting cells (APCs) in the colon were found post-PBio treatment, which correlated with LN Tfh. Finally, VSL#3 significantly down-modulated the response of TLR2, TLR3, TLR4 and TLR9-expressing HEK293 cells to stimulation with Pam3CSK4, Poly(I:C), LPS and ODN2006, respectively. These data provide a mechanism for the beneficial impact of PBio on mucosal health and implicates the use of PBio therapy in the context of vaccination or preventative approaches to enhance protection from mucosal infection by improving immune defenses at the mucosal portal of entry.

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“…To this end, new insight(s) on pathogen-host interaction have been obtained from recent ‘global-profiling’ of Chlamydia - and host-specific factors (Brotman et al 2014; Brunham and Rappuoli 2013). Transcriptome-wide or sequencing approaches have revealed the role for specific immune genes and associated pathways following infection with Ct-plasmid-sufficient and -deficient strains (Porcella et al 2015; Carlson et al 2008; Ferreira et al 2013; Qu et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Guinea pig genital tract lipidome reveals in vivo and in vitro regulation of phosphatidylcholine 16:0/18:1 and contribution to Chlamydia trachomatis serovar D infectivity

Wali

Gupta

et al. 2016

Metabolomics

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Introduction Chlamydia trachomatis (Ct), is the leading cause of sexually transmitted infections worldwide. Host transcriptomic- or proteomic profiling studies have identified key molecules involved in establishment of Ct infection or the generation of anti Ct-immunity. However, the contribution of the host metabolome is not known. Objectives The objective of this study was to determine the contribution of host metabolites in genital Ct infection. Methods We used high-performance liquid chromatography-mass spectrometry, and mapped lipid profiles in genital swabs obtained from female guinea pigs at days 3, 9, 15, 30 and 65 post Ct serovar D intravaginal infection. Results Across all time points assessed, 13 distinct lipid species including choline, ethanolamine and glycerol were detected. Amongst these metabolites, phosphatidylcholine (PC) was the predominant phospholipid detected from animals actively shedding bacteria i.e., at 3, 9, and 15 days post infection. However, at days 30 and 65 when the animals had cleared the infection, PC was observed to be decreased compared to previous time points. Mass spectrometry analyses of PC produced in guinea pigs (in vivo) and 104C1 guinea pig cell line (in vitro) revealed distinct PC species following Ct D infection. Amongst these, PC 16:0/18:1 was significantly upregulated following Ct D infection (p < 0.05, >twofold change) in vivo and in vitro infection models investigated in this report. Exogenous addition of PC 16:0/18:1 resulted in significant increase in Ct D in Hela 229 cells. Conclusion This study demonstrates a role for host metabolite, PC 16:0/18:1 in regulating genital Ct infection in vivo and in vitro.

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Microbiome, sex hormones, and immune responses in the reproductive tract: Challenges for vaccine development against sexually transmitted infections

Cited by 88 publications

References 119 publications

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function

Guinea pig genital tract lipidome reveals in vivo and in vitro regulation of phosphatidylcholine 16:0/18:1 and contribution to Chlamydia trachomatis serovar D infectivity

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