Reduced levels of genital tract immune biomarkers in postmenopausal women: implications for HIV acquisition

Abstract

Background: Rates of HIV infections are increasing in older adults. Although it is known that the HIV/AIDS epidemics affects women disproportionately, little is known regarding immune functions in the genital tract of postmenopausal women, as relevant to HIV susceptibility.

Objective: The objective of the study was to compare levels of female reproductive tract immune mediators that are important for HIV-associated immune responses as well as intrinsic anti-HIV activity in the cervical vaginal lavages collected from HIV-negative pre- and postmenopausal women.

Study design: Cervical vaginal lavage from 20 premenopausal and 20 postmenopausal women were assayed for interleukin-6, interleukin-8, tumor necrosis factor-α, secretory leukocyte protease inhibitor, elafin, human β-defensin-2, and macrophage inflammatory protein-3α using standard enzyme-linked immunosorbent assays. Anti-HIV activity of cervical-vaginal lavage was measured using TZM-bl indicator cells against HIV-1 IIIB and BaL. Whereas each postmenopausal woman provided only 1 sample, each premenopausal woman provided 3 samples, during proliferative, ovulatory, and secretory stages, based on menstrual dates.

Results: We observed significantly lower levels of tumor necrosis factor-α, MIP-3α, secretory leukocyte protease inhibitor, elafin, and human β-defensin-2 in cervical vaginal lavage from postmenopausal women compared with premenopausal women. Inhibition of HIV-1 infection was observed for both pre- and postmenopausal women, but cervical vaginal lavage from postmenopausal women showed significantly higher inhibition against HIV-1 BaL after adjusting for total protein concentration, genital pH, and reproductive tract infections. No change in mediators or HIV inhibition was observed through the stages of menstrual cycle. In addition, we observed that postmenopausal women with reproductive tract infections had significantly higher levels of tumor necrosis factor-α and significantly lower levels of interleukin-8, which were not observed in premenopausal women.

Conclusion: Our findings suggest that female reproductive tract immune microenvironment is distinct in HIV-negative postmenopausal women. Further studies are needed to assess the risk of HIV acquisition/transmission in this population.

Keywords: HIV; MIP-3α; antimicrobials; cervical vaginal lavage; female reproductive tract; menstrual cycle; mucosal factors; postmenopausal; secretory leukocyte protease inhibitor; tumor necrosis factor-α; β-defensin 2.