Lower Genital Tract Infections in HIV-Infected Women: Can We Afford to Miss?
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ABSTRACT:
SUBMITTER: Lallar M
PROVIDER: S-EPMC4342383 | biostudies-other | 2015 Feb
REPOSITORIES: biostudies-other
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Project description:IntroductionPrevious studies have shown that alterations of the bacterial microbiota in the lower female genital tract influence susceptibility to HIV infection and shedding. We assessed geographic differences in types of genital microbiota between HIV-infected and uninfected women from Rwanda and the United States.MethodsGenera of lower genital tract bacterial microbiota were identified by high-throughput pyrosequencing of the 16S rRNA gene from 46 US women (36 HIV-infected, 10 HIV-uninfected) and 40 Rwandan women (18 HIV-infected, 22 HIV-uninfected) with similar proportions of low (0-3) Nugent scores. Species of Lactobacillus were identified by assembling sequences along with reference sequences into phylogenetic trees. Prevalence of genera and Lactobacillus species were compared using Fisher's exact tests.ResultsOverall the seven most prevalent genera were Lactobacillus (74%), Prevotella (56%), Gardnerella (55%), Atopobium (42%), Sneathia (37%), Megasphaera (30%), and Parvimonas (26%), observed at similar prevalences comparing Rwandan to US women, except for Megasphaera (20% vs. 39%, p = 0.06). Additionally, Rwandan women had higher frequencies of Mycoplasma (23% vs. 7%, p = 0.06) and Eggerthella (13% vs. 0%, p = 0.02), and lower frequencies of Lachnobacterium (8% vs. 35%, p<0.01) and Allisonella (5% vs. 30%, p<0.01), compared with US women. The prevalence of Mycoplasma was highest (p<0.05) in HIV-infected Rwandan women (39%), compared to HIV-infected US women (6%), HIV-uninfected Rwandan (9%) and US (10%) women. The most prevalent lactobacillus species in both Rwandan and US women was L. iners (58% vs. 76%, p = 0.11), followed by L. crispatus (28% vs. 30%, p = 0.82), L. jensenii (20% vs. 24%, p = 0.80), L. gasseri (20% vs. 11%, p = 0.37) and L. vaginalis (20% vs. 7%, p = 0.10).DiscussionWe found similar prevalence of most major bacterial genera and Lactobacillus species in Rwandan and US women. Further work will be needed to establish whether observed differences differentially impact lower genital tract health or susceptibility to genital infections.
| S-EPMC4016010 | biostudies-literature
Project description:Samples were collected from infected female patients and RNA seq was used to determine the transcriptome of Neisseria gonorrhoeae both during infection and during growth in chemically defined media (CDM).
2015-07-21 | GSE71151 | GEO
Project description:BACKGROUND:Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity. METHODS:Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ? 2600 copies/mL (low viral load) (HIV-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). The CVL antimicrobial activity was also determined. RESULTS:Compared to HIV-uninfected participants, HIV-HVL women had higher levels of mucosal but not systemic proinflammatory cytokines and chemokines, higher Nugent scores, and lower Escherichia coli bactericidal activity. In contrast, there were no significant differences between HIV-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1?, MIP-1?, and CCL5 (RANTES) and higher plasma concentrations of MIP-1?. High PVL was associated with higher CVL levels of IL-1? and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking, and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model. CONCLUSIONS:Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.
| S-EPMC3706034 | biostudies-literature
Project description:Broadly neutralizing antibodies (bNAbs) targeting conserved epitopes on the HIV envelope glycoprotein have been identified in blood from HIV-1 infected women. We investigated whether antibodies in the genital tract from these women share similar epitope specificities and functional profiles as those in blood.Immunoglobulin (Ig)G and IgA antibodies were isolated from cervicovaginal lavages or Softcups from 13 HIV-infected women in the CAPRISA cohort using Protein G and Peptide M, respectively. Binding antibodies to envelope antigens were quantified by ELISA and binding antibody multiplex assay. Neutralizing antibody titers and epitope targets were measured using the TZM-bl assay with Env-pseudotyped wild-type and mutated viruses.HIV-specific IgG, but not IgA, was detected in genital secretions and the ratio of total IgG to HIV-specific IgG was similar to plasma. HIV-specific IgG reacted with multiple envelope antigens, including V1V2, gp120, gp140 and gp41. Two women had high plasma titers of HIV-specific IgG3 which was also detected in their genital tract samples. IgG from the genital tract had neutralizing activity against both Tier 1 and Tier 2 primary HIV-isolates. Antibodies targeting well known glycan epitopes and the membrane proximal region of gp41 were detected in genital secretions, and matched specificities in plasma.Women with plasma bNAbs have overlapping specificities in their genital secretions, indicating that these predominantly IgG isotype antibodies may transudate from blood to the genital tract. These data provide evidence that induction of systemic HIV-specific bNAbs can lead to antiviral immunity at the portal of entry.
| S-EPMC4816677 | biostudies-literature
Project description:Measurement of cytokines in the lower female genital tract offer insight into risk for HIV infection and reproductive complications. However, few studies have systematically compared mucosal collection methods or whether collection order matters. We compared longitudinal cytokine profiles in matched genital samples collected from women living with HIV using menstrual cup (MC), endocervical swabs (ECS) and swab-enriched cervicovaginal lavage (eCVL). Samples were collected at enrollment [MC:ECS:eCVL], 3-months (ECS:eCVL:MC) and 6-months (eCVL:MC:ECS) and concentrations of 28 cytokines determined by Luminex. Cytokine clustering was assessed using Principle Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLSDA) and factor analysis. Generally, higher cytokine concentrations were detected in MC samples, followed by ECS and eCVL, irrespective of study visit or sampling order. Factor analysis and PCA identified ECS to be inferior for measuring regulatory cytokines and IP-10 than eCVL or MC. Although concentrations differed, the majority of cytokines correlated between methods. Sampling order influenced cytokine concentrations marginally, and cytokines clustered more strongly by method than study visit. Variance in profiles was lowest in MC, suggesting greater consistency of sampling compared to other methods. We conclude that MC sampling offered advantages over other methods for detecting cytokines in women, with order marginally influencing profiles.
| S-EPMC6093917 | biostudies-literature
Project description:High-risk human papillomavirus (HR-HPV) is prevalent in HIV-infected women and may be associated with mucosal changes that promote HIV replication.Innate immune molecules, antimicrobial activity, HIV RNA, and HPV DNA genotypes were measured in a cross-sectional study of 128 HIV-infected women categorized into HPV-16 (n = 8), other HR-HPV (n = 41), and non-HR-HPV controls (n = 79).Compared to controls, HR-HPV groups had higher plasma viral loads (P = 0.004), lower CD4 cells (P = 0.02), more genital tract HIV RNA (P = 0.03), greater number of different HPV types (P < 0.001), higher cervicovaginal lavage (CVL) IL-1? (P = 0.03) and human beta-defensin 2 (HBD2) (P = 0.049), and less anti-HIVB al activity (P = 0.03). HPV-16 remained significantly associated with higher HBD2 (P = 0.03), higher IL-1? (P = 0.009), and lower anti-HIVB aL activity (P = 0.03) compared to controls after adjusting for plasma viral load and CD4 T cell count.HR-HPV is associated with mucosal changes in HIV-infected women that could adversely impact genital tract health.
| S-EPMC4715979 | biostudies-literature
Project description:Initiation of highly active antiretroviral therapy (HAART) for HIV-infected individuals is associated with control of viremia, improved CD4 counts, and declining systemic HIV-specific immune responses. While HAART effectively reduces plasma viremia, it remains unclear how effectively antiretroviral drugs reach mucosal surfaces, such as those of the genital tract. The aim of this study was to determine the effect of HAART on genital tract CD4 T cell reconstitution, HIV shedding, and HIV-specific T cell responses. Cervical cytobrush and blood specimens were obtained from 35 HIV-infected, HAART-naïve women and 27 women on HAART in order to investigate HIV Gag-specific T cell responses by intracellular gamma interferon (IFN-γ) staining. Interleukin 1β (IL-1β), IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assays (ELISA). We show that for HIV-infected women, HAART is associated with significantly improved CD4 T cell counts both in blood and at the cervix. While HAART effectively suppressed both blood and cervical viremia, HIV-specific CD8 T cell responses in blood were lost, while those at the cervix were preserved.
| S-EPMC2950605 | biostudies-literature
Project description:Gonorrhea is a highly prevalent disease resulting in significant morbidity worldwide, with an estimated 106 cases reported annually. Neisseria gonorrhoeae, the causative agent of gonorrhea, colonizes and infects the human genital tract and often evades host immune mechanisms until successful antibiotic treatment is used. The alarming increase in antibiotic-resistant strains of N. gonorrhoeae, the often asymptomatic nature of this disease in women and the lack of a vaccine directed at crucial virulence determinants have prompted us to perform transcriptome analysis to understand gonococcal gene expression patterns during natural infection. We sequenced RNA extracted from cervico-vaginal lavage samples collected from women recently exposed to infected male partners and determined the complete N. gonorrhoeae transcriptome during infection of the lower genital tract in women. On average, 3.19% of total RNA isolated from female samples aligned to the N. gonorrhoeae NCCP11945 genome and 1750 gonococcal ORFs (65% of all protein-coding genes) were transcribed. High expression in vivo was observed in genes encoding antimicrobial efflux pumps, iron response, phage production, pilin structure, outer membrane structures and hypothetical proteins. A parallel analysis was performed using the same strains grown in vitro in a chemically defined media (CDM). A total of 140 genes were increased in expression during natural infection compared to growth in CDM, and 165 genes were decreased in expression. Large differences were found in gene expression profiles under each condition, particularly with genes involved in DNA and RNA processing, iron, transposase, pilin and lipoproteins. We specifically interrogated genes encoding DNA binding regulators and iron-scavenging proteins, and identified increased expression of several iron-regulated genes, including tbpAB and fbpAB, during infection in women as compared to growth in vitro, suggesting that during infection of the genital tract in women, the gonococcus is exposed to an iron deplete environment. Collectively, we demonstrate that a large portion of the gonococcal genome is expressed and regulated during mucosal infection including genes involved in regulatory functions and iron scavenging.
| S-EPMC4526530 | biostudies-literature
Project description:Women with polycystic ovarian syndrome (PCOS) often have a history of infertility and poor pregnancy outcome. The character of the lower genital tract (LGT) microbiome of these patients is still unknown. We collected both vaginal and cervical canal swabs from 47 PCOS patients (diagnosed by the Rotterdam Criteria) and 50 healthy reproductive-aged controls in this study. Variable regions 3-4 (V3-4) were sequenced and analyzed. Operational taxonomic unit (OTU) abundance was noted for all samples. Taxa that discriminated between PCOS and healthy women was calculated by linear discriminant analysis effect size (LEFSe). Results from 97 paired vaginal and cervical canal samples collected from 97 women [mean age 30 (±4 years)] were available for analysis. Using the Rotterdam Criteria, 47 women were diagnosed with PCOS (PCOS, n = 47; control, n = 50). There was no significant difference between cervical canal microbiome and vaginal microbiome from the same individual, however, Lactobacillus spp. was less abundant in both vaginal and cervical canal microbiome of PCOS patients. Several non-Lactobacillus taxa including Gardnerella_vaginalis_00703mash, Prevotella_9_other, and Mycoplasma hominis, were more abundant in the LGT microbiota of PCOS patients. There is a difference between the microorganism in the LGT of patients with PCOS and healthy reproductive-aged women.
| S-EPMC7506141 | biostudies-literature
Project description:During infection, Neisseria gonorrhoeae senses and responds to stress; such responses may be modulated by MisRS (NGO0177 and NGO0176), a two-component system that is a homolog of CpxRA. In Escherichia coli, CpxRA senses and responds to envelope stress; CpxA is a sensor kinase/phosphatase for CpxR, a response regulator. When a cpxA mutant is grown in medium containing glucose, CpxR is phosphorylated by acetyl phosphate but cannot be dephosphorylated, resulting in constitutive activation. Kandler and coworkers (J. L. Kandler, C. L. Holley, J. L. Reimche, V. Dhulipala, J. T. Balthazar, A. Muszyński, R. W. Carlson, and W. M. Shafer, Antimicrob Agents Chemother 60:4690-4700, 2016, https://doi.org/10.1128/AAC.00823-16) showed that MisR (CpxR) is required for the maintenance of membrane integrity and resistance to antimicrobial peptides, suggesting a role in gonococcal survival in vivo Here, we evaluated the contributions of MisR and MisS (CpxA) to gonococcal infection in a murine model of cervicovaginal colonization and identified MisR-regulated genes using RNA sequencing (RNA-Seq). The deletion of misR or misS severely reduced the capacity of N. gonorrhoeae to colonize mice or maintain infection over a 7-day period and reduced microbial fitness after exposure to heat shock. Compared to the wild type (WT), the inactivation of misR identified 157 differentially regulated genes, most of which encoded putative envelope proteins. The inactivation of misS identified 17 differentially regulated genes compared to the WT and 139 differentially regulated genes compared to the misR mutant, 111 of which overlapped those differentially expressed in the comparison of the WT versus the misR mutant. These data indicate that an intact MisRS system is required for gonococcal infection of mice. Provided the MisR is constitutively phosphorylated in the misS mutant, the data suggest that controlled but not constitutive activation is required for gonococcal infection in mice.
| S-EPMC5563589 | biostudies-literature