Abstract
Approximately 40% of global HIV-1 transmission occurs in the female genital tract (FGT) through heterosexual transmission. Epithelial cells lining the FGT provide the first barrier to HIV-1 entry. Previous studies have suggested that certain hormonal contraceptives or a dysbiosis of the vaginal microbiota can enhance HIV-1 acquisition in the FGT. We examined the effects of lactobacilli and female sex hormones on the barrier functions and innate immune responses of primary endometrial genital epithelial cells (GECs). Two probiotic strains, Lactobacillus reuteri RC-14 and L. rhamnosus GR-1, were tested, as were sex hormones estrogen (E2), progesterone (P4), and the hormonal contraceptive medroxyprogesterone acetate (MPA). Our results demonstrate that probiotic lactobacilli enhance barrier function without affecting cytokines. Treatment of GECs with MPA resulted in reduced barrier function. In contrast, E2 treatment enhanced barrier function and reduced production of proinflammatory cytokines. Comparison of hormones plus lactobacilli as a pre-treatment prior to HIV exposure revealed a dominant effect of lactobacilli in preventing loss of barrier function by GECs. In summary, the combination of E2 and lactobacilli had the best protective effect against HIV-1 seen by enhancement of barrier function and reduction in proinflammatory cytokines. These studies provide insights into how probiotic lactobacilli in the female genital microenvironment can alter HIV-1-mediated barrier disruption and how the combination of E2 and lactobacilli may decrease susceptibility to primary HIV infection.
Highlights
Women account for more than 50% of people infected with HIV-1 worldwide [1]
After a further h of culture, barrier function was assessed by Fluorescein Isothiocyanate (FITC)-dextran leakage and transepithelial resistance (TER), a measure of cell to the basolateral compartment beneath the genital epithelial cells (GECs) monolayers treated with probiotic lactobacilli, compared to the control cultures without bacteria (Figure 1B)
Both decrease in permeability and the increase in TER indicates that probiotic lactobacilli were able to enhance GEC barrier functions
Summary
Women account for more than 50% of people infected with HIV-1 (human immunodeficiency virus-1) worldwide [1]. The number of new HIV-1 infections reported in women has risen continuously over the past few decades and women have been shown to be at an increased risk of HIV-1 infection compared to men [1]. Infection in women occurs primarily through heterosexual transmission in the female genital tract (FGT) with early mechanisms still not well understood [2]. The etiology of greater acquisition within the FGT is not fully understood, increased inflammation in the FGT has been suggested as a common theme associated with higher rates of. The FGT can be divided into two distinct compartments. The lower FGT consists of the vagina and the ectocervix and is protected by multiple layers of stratified squamous epithelium
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