Dataset Information

Bacterial Vaginosis Is Associated with Loss of Gamma Delta T Cells in the Female Reproductive Tract in Women in the Miami Women Interagency HIV Study (WIHS): A Cross Sectional Study.

ABSTRACT: Bacterial vaginosis (BV) is the most common female reproductive tract infection and is associated with an increased risk of acquiring and transmitting HIV by a mechanism that is not well understood. Gamma delta (GD) T cells are essential components of the adaptive and innate immune system, are present in the female reproductive tract, and play an important role in epithelial barrier protection. GD1 cells predominate in the mucosal tissue and are important in maintaining mucosal integrity. GD2 cells predominate in peripheral blood and play a role in humoral immunity and in the immune response to pathogens. HIV infection is associated with changes in GD T cells frequencies in the periphery and in the female reproductive tract. The objective of this study is to evaluate if changes in vaginal flora occurring with BV are associated with changes in endocervical GD T cell responses, which could account for increased susceptibility to HIV. Seventeen HIV-infected (HIV+) and 17 HIV-uninfected (HIV-) pre-menopausal women underwent collection of vaginal swabs and endocervical cytobrushes. Vaginal flora was assessed using the Nugent score. GD T cells were assessed in cytobrush samples by flow cytometry. Median Nugent score was 5.0 and 41% of women had abnormal vaginal flora. In HIV uninfected women there was a negative correlation between Nugent score and cervical GD1 T cells (b for interaction = - 0.176, p<0.01); cervical GD1 T cells were higher in women with normal vaginal flora than in those with abnormal flora (45.00% vs 9.95%, p = 0.005); and cervical GD2 T cells were higher in women with abnormal flora than in those with normal flora (1.70% vs 0.35%, p = 0.023). GD T cells in the genital tract are protective (GD1) and are targets for HIV entry (GD2). The decrease in cervical GD1 and increase in GD2 T cells among women with abnormal vaginal flora predisposes women with BV to HIV acquisition. We propose to use GD T cell as markers of female genital tract vulnerability to HIV.

SUBMITTER: Alcaide ML

PROVIDER: S-EPMC4831836 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Bacterial Vaginosis Is Associated with Loss of Gamma Delta T Cells in the Female Reproductive Tract in Women in the Miami Women Interagency HIV Study (WIHS): A Cross Sectional Study.

Alcaide Maria L ML Strbo Natasa N Romero Laura L Jones Deborah L DL Rodriguez Violeta J VJ Arheart Kristopher K Martinez Octavio O Bolivar Hector H Podack Eckhard R ER Fischl Margaret A MA

PloS one 20160414 4

Bacterial vaginosis (BV) is the most common female reproductive tract infection and is associated with an increased risk of acquiring and transmitting HIV by a mechanism that is not well understood. Gamma delta (GD) T cells are essential components of the adaptive and innate immune system, are present in the female reproductive tract, and play an important role in epithelial barrier protection. GD1 cells predominate in the mucosal tissue and are important in maintaining mucosal integrity. GD2 ce ...[more]

PMID: 27078021

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Project description:Cardiovascular disease (CVD) is a major comorbidity among HIV-infected individuals. Common carotid artery intima-media thickness (cCIMT) is a valid and reliable subclinical measure of atherosclerosis and is known to predict CVD. We performed genome-wide association (GWA) and admixture analysis among 682 HIV-positive and 288 HIV-negative Black, non-Hispanic women from the Women's Interagency HIV study (WIHS) cohort using a combined and stratified analysis approach. We found some suggestive associations but none of the SNPs reached genome-wide statistical significance in our GWAS analysis. The top GWAS SNPs were rs2280828 in the region intergenic to mediator complex subunit 30 and exostosin glycosyltransferase 1 (MED30 | EXT1) among all women, rs2907092 in the catenin delta 2 (CTNND2) gene among HIV-positive women, and rs7529733 in the region intergenic to family with sequence similarity 5, member C and regulator of G-protein signaling 18 (FAM5C | RGS18) genes among HIV-negative women. The most significant local European ancestry associations were in the region intergenic to the zinc finger and SCAN domain containing 5D gene and NADH: ubiquinone oxidoreductase complex assembly factor 1 (ZSCAN5D | NDUF1) pseudogene on chromosome 19 among all women, in the region intergenic to vomeronasal 1 receptor 6 pseudogene and zinc finger protein 845 (VN1R6P | ZNF845) gene on chromosome 19 among HIV-positive women, and in the region intergenic to the SEC23-interacting protein and phosphatidic acid phosphatase type 2 domain containing 1A (SEC23IP | PPAPDC1A) genes located on chromosome 10 among HIV-negative women. A number of previously identified SNP associations with cCIMT were also observed and included rs2572204 in the ryanodine receptor 3 (RYR3) and an admixture region in the secretion-regulating guanine nucleotide exchange factor (SERGEF) gene. We report several SNPs and gene regions in the GWAS and admixture analysis, some of which are common across HIV-positive and HIV-negative women as demonstrated using meta-analysis, and also across the two analytic approaches (i.e., GWA and admixture). These findings suggest that local European ancestry plays an important role in genetic associations of cCIMT among black women from WIHS along with other environmental factors that are related to CVD and may also be triggered by HIV. These findings warrant confirmation in independent samples.

Project description:AIMS:To test whether human immunodeficiency virus (HIV) infection and subclinical cardiovascular disease (sCVD) are associated with expression of CXCR4 and other surface markers on classical, intermediate, and non-classical monocytes in women. METHODS AND RESULTS:sCVD was defined as presence of atherosclerotic lesions in the carotid artery in 92 participants of the Women's Interagency HIV Study (WIHS). Participants were stratified into four sets (n?=?23 each) by HIV and sCVD status (HIV-/sCVD-, HIV-/sCVD+, HIV+/sCVD-, and HIV+/sCVD+) matched by age, race/ethnicity, and smoking status. Three subsets of monocytes were determined from archived peripheral blood mononuclear cells. Flow cytometry was used to count and phenotype surface markers. We tested for differences by HIV and sCVD status accounting for multiple comparisons. We found no differences in monocyte subset size among the four groups. Expression of seven surface markers differed significantly across the three monocyte subsets. CXCR4 expression [median fluorescence intensity (MFI)] in non-classical monocytes was highest among HIV-/CVD- [628, interquartile range (IQR) (295-1389)], followed by HIV+/CVD- [486, IQR (248-699)], HIV-/CVD+ (398, IQR (89-901)), and lowest in HIV+/CVD+ women [226, IQR (73-519)), P?=?0.006 in ANOVA. After accounting for multiple comparison (Tukey) the difference between HIV-/CVD- vs. HIV+/CVD+ remained significant with P?=?0.005 (HIV-/CVD- vs. HIV+/CVD- P?=?0.04, HIV-/CVD- vs. HIV-/CVD+ P?=?0.06, HIV+/CVD+ vs. HIV+/CVD- P?=?0.88, HIV+/CVD+ vs. HIV-/CVD+ P?=?0.81, HIV+/CVD- vs. HIV-/CVD+, P?=?0.99). All pairwise comparisons with HIV-/CVD- were individually significant (P?=?0.050 vs. HIV-/CVD+, P?=?0.028 vs. HIV+/CVD-, P?=?0.009 vs. HIV+/CVD+). CXCR4 expression on non-classical monocytes was significantly higher in CVD- (501.5, IQR (249.5-887.3)) vs. CVD+ (297, IQR (81.75-626.8) individuals (P?=?0.028, n?=?46 per group). CXCR4 expression on non-classical monocytes significantly correlated with cardiovascular and HIV-related risk factors including systolic blood pressure, platelet and T cell counts along with duration of antiretroviral therapy (P?<?0.05). In regression analyses, adjusted for education level, study site, and injection drug use, presence of HIV infection and sCVD remained significantly associated with lower CXCR4 expression on non-classical monocytes (P?=?0.003), but did not differ in classical or intermediate monocytes. CONCLUSION:CXCR4 expression in non-classical monocytes was significantly lower among women with both HIV infection and sCVD, suggesting a potential atheroprotective role of CXCR4 in non-classical monocytes.

Dataset Information

Bacterial Vaginosis Is Associated with Loss of Gamma Delta T Cells in the Female Reproductive Tract in Women in the Miami Women Interagency HIV Study (WIHS): A Cross Sectional Study.

Publications

Bacterial Vaginosis Is Associated with Loss of Gamma Delta T Cells in the Female Reproductive Tract in Women in the Miami Women Interagency HIV Study (WIHS): A Cross Sectional Study.

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