Cross-Sectional Analysis of Selected Genital Tract Immunological Markers and Molecular Vaginal Microbiota in Sub-Saharan African Women, with Relevance to HIV Risk and Prevention

Abstract

There is a paucity of data on the clinical and epidemiological factors associated with immunological markers and consequently risk of HIV acquisition in various groups of women from SSA. Hormonal variation during the menstrual cycle is accompanied by a transient immune suppression that is necessary to ensure successful fertilization and embryo implantation in the uterus (4). Hormonal differences may result in different mucosal immunological profiles in pregnant women (5, 6) and adolescent girls compared to nonpregnant adult women. Differential exposure to mucosal infections (7) and other behavioral factors that alter HIV acquisition risk such as traditional vaginal practices and having multiple sexual partners might also have an impact on mucosal immunology in the FGT. SSA has the highest prevalence of bacterial vaginosis (BV) (8), which has been associated with greater susceptibility to HIV infection (9) and increased female-to-male HIV-1 transmission (10). All of these factors work in concert and

The Human Microbiome during Bacterial Vaginosis

“…Later, Doerflinger et al confirmed that P. bivia increased the levels of MIP-3␣ and also IL-1␤ in vitro (85). Clinically, P. bivia was associated with higher cervicovaginal levels of IL-1␤ (72,74) and and with the most proinflammatory (highest levels of IL-1␣, IL-1␤, and TNF-␣) cervical microbiota community type in African women (75).…”

“…Although inconsistent effects on cytokines, e.g., IL-6 and TNF-␣, have been reported (69,85) (70). In clinical studies, the detection of A. vaginae in vaginal swabs was correlated with higher levels of the same inflammatory mediators that were associated with G. vaginalis (74), and Atopobium was among the taxa most abundant in microbiota community types distinguished by the highest levels of cervicovaginal inflammatory mediators in a study of South African women (75).…”

“…Similarly, genomic PCR analysis of vaginal swabs implicated G. vaginalis in increased cervicovaginal levels of IL-1␤ and other proinflammatory cytokines, e.g., IL-1␣, IL-6, IL-8, and IL-12p70, even though some immunosuppressive effects, e.g., reduced levels of interferon gamma-induced protein 10 (IP-10) and SLPI, were also observed (74). G. vaginalis was also one of the six dominant species identified by 16S rRNA gene sequencing in a microbiota community type distinguished by higher cervicovaginal levels of IL-1␣, IL-␤, IL-8, TNF-␣, IFN-␥, and IL-10 in young South Africans at risk of HIV (75).…”

“…In women with aerobic vaginitis, the number of vaginal leukocytes on wet mounts positively correlated with vaginal levels of IL-1␤ (123), suggesting that higher levels of IL-1␤ in women with BV are not sufficient to drive the same leukocyte response as that in women with aerobic vaginitis or that BV organisms reduce leukocyte recruitment or half-life by mechanisms that are yet to be defined. BV has also been associated with a significant reduction in vaginal levels of the secretory leukocyte protease inhibitor (SLPI), which is produced by both epithelial and immune cells (74,(124)(125)(126).…”

Impact of Hydroxychloroquine-Loaded Polyurethane Intravaginal Rings on Lactobacilli

“…Among the normal vaginal flora protecting the FGT, lactobacilli represent the main type of bacteria that establish the balance between pathogenic bacteria and healthy flora. Decreases in lactobacilli encourage overgrowth of pathogenic bacteria and can lead to inflammation and susceptibility to various sexually transmitted diseases (26)(27)(28). Therefore, it is very important to assess the toxic effects of microbicides on lactobacilli, as well as their effects on vaginal epithelial cell monolayer integrity, to ensure that the microbicides do not disrupt the complex microenvironment.…”