Search

Objective: Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration. Study Design: Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA. Results: IL-8 cleaving/altering activity was observed in fluids from both HIV-positive (28%) and HIV-negative women (35%). There was no clear relationship between the activity and the types of bacteria present in the lower genital tract as determined by high-throughput sequencing of the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases (MMPs) reduced the activity and a multiplex assay that detects both inactive and active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, -9, -10 and -12 in genital secretions from many of the women. The IL-8-cleaving/altering activity significantly correlated with active MMP-9 as well as with cleavage of a substrate that is acted on by several active MMPs. Conclusions: These studies show that multiple MMPs are present in the genital tract of women and strongly suggest that MMP-9 in genital secretions can cleave IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL-8 can modulate inflammatory responses in the lower genital tract. [ABSTRACT FROM AUTHOR]

Background. Whether human immunodeficiency virus (HIV) infection is associated with a change in the diversity of genital microbiota in women was investigated. Methods. Amplicon length heterogeneity polymerase chain reaction (LH-PCR) analysis and pyrosequencing of the 16S ribosomal RNA gene were used to analyze the diversity of the microbiota in HIV-positive (HIV+) and HIV-negative (HIV-) women with or without bacterial vaginosis (BV). Results. LH-PCR analysis revealed significantly more microbiota diversity in BV-positive (BV+) women than in BV-negative (BV-) women, but no significant difference was noted between HIV+ women and HIV- women. Pyrosequencing revealed that Lactobacillus organisms constituted a median of 96% of the bacteria in BV- women. BV+ women had a significantly higher number of taxa found at ⩾1% of the total genital microbiota (median, 11 taxa). Commontaxa in BV+ women were Prevotella, Megasphaera, Gardnerella, Coriobacterineae, Lachnospira, and Sneathia. There was a trend (P = .07) toward the presence of a higher number of taxa in HIV+BV+ women than in HIV-BV+ women. Propionibacterineae, Citrobacter, and Anaerococcus were the taxa found only in HIV+ women (P <.05). Conclusions. The present study demonstrated that both LH-PCR analysis and pyrosequencing differentiated microbiota in BV+ women from that in BV- women and that pyrosequencing indicated a trend toward increased diversity in BV+HIV+ women, suggesting that HIV infection is associated with changes in the diversity of genital microbiota. [ABSTRACT FROM AUTHOR]

The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at ≥1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P < .001) or with concomitant genital tract infection (P = .003). Endocervical canal wicks should be considered as an adjunct to cervicovaginal lavage, to improve the sensitivity and precision of HIV-1 RNA detection. [ABSTRACT FROM AUTHOR]