Immune Responses to HIV in the Female Reproductive Tract, Immunologic Parallels with the Gastrointestinal Tract, and Research Implications

Abstract

Citation Shacklett BL, Greenblatt RM. Immune responses to HIV in the female reproductive tract, immunologic parallels with the gastrointestinal tract, and research implications. Am J Reprod Immunol 2011; 65: 230–241 The female reproductive tract is a major site of mucosa‐associated lymphoid tissue and susceptibility to HIV infection, yet the tissue site(s) of infection and the impact of HIV infection on this important mucosal tissue remain poorly understood. CD4+ T cells and other cell types expressing the major coreceptors for HIV, CCR5, and CXCR4 are abundant in both the lower reproductive tract (endocervix and vagina) and the upper tract (endocervix and uterus) and are highly susceptible to infection. Antiviral defenses in the female reproductive tract are mediated by a variety of soluble factors and by mucosal effector cells that differ phenotypically from their counterparts in blood. The immunologic characteristics of the female reproductive tract parallel those of the gut, where major HIV‐related immunologic injury occurs. The susceptibility of the female reproductive tract to HIV infection and immunopathogenesis suggests important new avenues for further research.

Anatomic and Hormonal Changes in the Female Reproductive Tract Immune Environment during the Life Cycle: Implications for HIV/STI Prevention Research

“…4 It is plausible that virological, immunologic, and microbiological parameters that affect HIV-1 pathogenesis and transmission may vary in the setting of evolving anatomic structures and fluctuations in female reproductive hormones through the life cycle. 3,5,6 This review provides a conceptual overview of anatomic and hormonal changes in the female reproductive tract from adolescence through menopause to contextualize other articles in this special edition of AJRI (See Table I). We highlight clinically relevant changes in the female reproductive tract that are mediated by estradiol and progesterone and the menstrual cycle, and how these changes may affect mucosal immunology and susceptibility to HIV and sexually transmitted infections (STIs) across the female life cycle.…”

Mycoplasma genitalium promotes epithelial crossing and peripheral blood mononuclear cell infection by HIV-1

“…We used the dual chamber Transwell culturing format for in vitro modeling of female genital–mucosal tissues, with the lumen represented by the insert well chamber, the epithelium by epithelial monolayers grown on the semipermeable bottoms of the insert wells, and the bottom wells supplying a microenvironment similar to the subepithelial lamina propria. 14–16 Using this layered cell culturing format, we asked (1) whether M. genitalium infection of the epithelium amplifies the movement of HIV through the epithelium, and (2) whether the presence of M. genitalium -infected epithelial cells amplifies the infectivity and replication of HIV in peripheral blood mononuclear cells (PBMC).…”

Mucosal Immunity to HIV-1

“…This IgA has been reported to neutralize primary HIV-1 strains in vitro and to block viral transcytosis across an intact monolayer of cultured epithelial cells. However, this topic remains controversial, as other studies of HEPS cohorts have failed to detect such antibodies in secretions (Shacklett and Greenblatt 2011).…”

“…Other sexually transmitted infections (STI), including C. trachomatis, chancroid (H. ducreyi), and herpes simplex viruses, can increase susceptibility to HIV-1 transmission by increasing local inflammation, recruiting infectable target cells, and through other mechanisms. Bacterial vaginosis may also facilitate HIV-1 transmission (Shacklett and Greenblatt 2011).…”