Toll-like receptor gene variants and bacterial vaginosis among HIV-1 infected and uninfected African women

Mackelprang, Romel D.; Scoville, Caitlin W; Cohen, Craig R.; Ondondo, Raphael; Bigham, Abigail W.; Celum, Connie; Campbell, Mary S.; Essex, M.; Wald, Anna; Kiarie, James; Ronald, Allan R.; Gray, Glenda; Lingappa, Jairam R.

doi:10.1038/gene.2015.13

Cited by 20 publications

(16 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…; Mackelprang et al . ). Women with CST‐IV‐like states show significant increases in IL‐1α, IL‐1β, TNF‐α, IFN‐γ, IL‐4, IL‐8, IL‐10, IL‐12p70, and fms‐like tyrosine kinase 3 ligand relative to CST‐I as well as significantly higher IFN‐γ in CST‐III relative to CST‐I.…”

Section: Introductionmentioning

confidence: 97%

The vaginal microbiota, host defence and reproductive physiology

Smith

Ravel

2016

The Journal of Physiology

283

225

View full text Add to dashboard Cite

The interaction between the human host and the vaginal microbiota is highly dynamic. Major changes in the vaginal physiology and microbiota over a woman's lifetime are largely shaped by transitional periods such as puberty, menopause and pregnancy, while daily fluctuations in microbial composition observed through culture-independent studies are more likely to be the results of daily life activities and behaviours. The vaginal microbiota of reproductive-aged women is largely made up of at least five different community state types. Four of these community state types are dominated by lactic-acid producing Lactobacillus spp. while the fifth is commonly composed of anaerobes and strict anaerobes and is sometimes associated with vaginal symptoms. The production of lactic acid has been associated with contributing to the overall health of the vagina due to its direct and indirect effects on pathogens and host defence. Some species associated with non-Lactobacillus vaginal microbiota may trigger immune responses as well as degrade the host mucosa, processes that ultimately increase susceptibility to infections and contribute to negative reproductive outcomes such as infertility and preterm birth. Further studies are needed to better understand the functional underpinnings of how the vaginal microbiota affect host physiology but also how host physiology affects the vaginal microbiota. Understanding this fine-tuned interaction is key to maintaining women's reproductive health.

show abstract

Section: Introductionmentioning

confidence: 97%

The vaginal microbiota, host defence and reproductive physiology

Smith

Ravel

2016

The Journal of Physiology

283

225

View full text Add to dashboard Cite

show abstract

“…As summarized in Supplementary Table 1, several investigators have found polymorphisms in TLR genes related to altered risk of BV and enrichment of BV-related bacteria. TLRs, especially TLR2 alone or in combination with TLR-1/TLR-6 and TLR-4, have been recognized for their association with BV and BVrelated bacteria, as these TLRs precipitate release of pro-inflammatory cytokines and recruitment of inflammatory cells [43][44][45][46][47]. As summarized by Taylor et al, TLR gene variants can lead to inadequate or excess inflammatory immune response, which can affect disease susceptibility or progression [44].…”

Section: Discussionmentioning

confidence: 99%

Host Genetic Determinants of the Vaginal Microbiome in Kenyan Women

Mehta

Nannini²,

Otieno

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Women with vaginal microbial community state types (CST) with high diversity and a paucity of Lactobacillus crispatus have increased risk of HIV acquisition. Identifying host genetic factors associated with the vaginal microbial composition may aid in elucidating the biological mechanisms regulating these microbial traits and inter-individual variations in associated diseases. Methods We conducted genome-wide associations studies (GWASs) on vaginal microbiome traits on 171 Kenyan women. Study participants were genotyped using the Infinium Global Screening Array and 16S rRNA gene amplicon sequencing was performed to characterize the vaginal microbiome. Linear and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between L. crispatus, L. iners, G. vaginalis, Shannon diversity index, and CST with host genetic single nucleotide polymorphisms (SNPs). Pathway enrichment analyses were performed to identify biological processes putatively associated with the vaginal microbiome traits. Results At baseline, the median age of study participants was 22 years (IQR: 22 – 25) with 22% having Bacterial vaginosis (Nugent score 7-10). L. crispatus and L. iners were present in 24% and 83% of samples with a mean relative abundance of 31% and 45%, respectively. The most significant SNPs associated were: rs73330467 located between LOC101927488-GRAMD2B ( P =4.79x10 -6 ) for L. crispatus ; rs527430 in the FOXD2-TRABD2B ( P =6.98x10 -7 ) region for L. iners ; rs1229660 in the SNX10-LOC441204 ( P =4.65x10 -6 ) region for G. vaginalis; rs972741 in the ZKSCAN2-HS3ST4 ( P =8.52x10 -7 ) region for Shannon diversity index; and rs2302902 in ELK3 ( P =3.09x10 -6 ) for CST. During pathway enrichment analysis, Toll-like receptors, cytokine production, and other components of innate immune response were associated with L. crispatus, L. iners, and CST. Multiple genomic loci were replicated, including IL-8 (Shannon, CST), TIRAP ( L. iners , Shannon), TLR2 (Shannon, CST), MBL2 ( L. iners , G. vaginalis , CST), and MYD88 ( L. iners, Shannon). Conclusions We identified numerous genetic loci on several pathways related to host immunity and infection that were associated with vaginal microbiome traits, providing insight into potential host genetic influences on vaginal microbiome composition. This new information should guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals, and across populations.

show abstract

“…All tests were performed using Review Manager (RevMan version 5.3.0) software and two-sided p value < 0.05 was considered statistically significant. Djigma 2011 [34] Nowark 2011 [45] Gallo 2011 [40] Oliveira 2011 [17] Chiduo 2012 [30] Blitz 2013 [36] Hu 2013 [18] Apalata 2014 [20] Benning 2014 [41] Mackelprang 2015 [43] Masson 2015 [42] Alczuk 2015 [15] Massad 2016 [37] Reimers 2016 [38] Kriek 2016 [46] Alcaide 2016 [14] :High risk of bias: Unclear risk of bias: Low risk of bias…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of The Prevalence of Genital Infections Among Hiv Carriers and Uninfected Women

Costa¹,

Santos²,

Sarmento³

et al. 2018

TOAIDJ

View full text Add to dashboard Cite

Background & Aim:The risk factors in acquiring genital co-infections associated with HIV infection still present many questions. We conducted a systematic review and meta-analysis to compare the prevalence of genital infection among HIV-infected and uninfected women.Methods:We searched PubMed, Web of Science, Scopus and Scielo for the relevant studies up until October 2017. Data were collected from the included studies and methodologically assessed. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using fixed or random-effects models.Results:Thirty-six articles involving 23,863 women with retroviruses were included. HIV-infected women were significantly more diagnosed with the following genital infections:Herpes simplexvirus type 2 (HSV-2) (OR 3.70; 95% CI: 2.42–5.65),Neisseria gonorrhoeae(GC) (OR 4.18; 95% CI: 2.15-8.13),Chlamydia trachomatis(CT) (OR 2.25; 95% CI: 1.20-4.23) and Human papillomavirus (HPV) (OR 3.99, 95% CI: 3.35-4.75). There was no significant difference in the prevalence of bacterial vaginosis (OR 1.09; 95% CI: 0.91-1.30),Candida sp. (OR 1.51; 95% CI: 0.71-3.25),Treponema pallidum(OR 1.56; 95% CI: 1.00-2.45) andTrichomonas vaginalis(OR 1.00; 95% CI: 0.47-2.15).Conclusion:The prevalence of HPV, HSV-2, GC and CT genital infection was significantly higher among HIV-positive women.

show abstract

Toll-like receptor gene variants and bacterial vaginosis among HIV-1 infected and uninfected African women

Cited by 20 publications

References 23 publications

The vaginal microbiota, host defence and reproductive physiology

The vaginal microbiota, host defence and reproductive physiology

Host Genetic Determinants of the Vaginal Microbiome in Kenyan Women

Meta-Analysis of The Prevalence of Genital Infections Among Hiv Carriers and Uninfected Women

Contact Info

Product

Resources

About