Role of Mucosal Immunity in Preventing Genital Herpes Infection

Abstract

The female genital tract is immunologically unique because it must be tolerant to spermatozoa, pregnancy, and vaginal flora, but also protect the host from pathogen challenge. The mucosal response to herpes simplex viruses (HSV), a major cause of genital ulcerative disease and critical co-factor in the HIV/AIDS epidemic, is complex and consists of the normally acidic vaginal environment, constitutively secreted and induced antimicrobial peptides, complement, and cellular responses mediated by epithelial and immune cells. This review summarizes our current understanding of the mucosal response to HSV focusing on those factors that may prevent initial infection. Understanding how each of these components contribute to innate immunity, mechanisms of antiviral activity, and whether the virus has evolved strategies to evade their effects may lead to the development of novel vaginal microbicides.

Antiviral Activity of Trappin-2 and Elafin In Vitro and In Vivo against Genital Herpes

“…An indirect inhibitory anti-HSV-2 effect of SLPI would support our data, since SLPI was found to exert its protective antiviral effect by interacting through ECs and not virus (70). However, the involvement of annexin II in anti-HSV-2 defense, which was important for anti-HIV-1 activity of SLPI, was ruled out (25). The observed inhibitory effect of Tr/E on HSV-2 attachment may have significant implications, since viral attachment to ECs is one of the critical steps required for subsequent fusion and entry of HSV-2 into ECs.…”

“…Serine protease inhibitor elafin (E) and its precursor, trappin-2 (Tr), along with secretory leukocyte protease inhibitor (SLPI) and defensins, belong to a large family of cationic antimicrobials that have been linked to endogenous mucosal protection against sexually transmitted pathogens, including HSV-2 and HIV-1 (23)(24)(25)(26). Trappin-2 and elafin (Tr/E), as well as SLPI, share the cysteine-rich fold with four disulfide bonds called the whey acidic protein (WAP) domain, involved in protease inhibition (27).…”

Comprehensive Proteomic Analysis of Human Cervical−Vaginal Fluid

“…40 Additionally, we have also detected several proteins from the histone family (H4, H2A, H2B, and H1.2). Traditionally, histones are considered to be intracellular proteins that are involved in chromatin arrangement inside the nucleus.…”

Mucosa-Associated Epithelial Chemokine/CCL28 Expression in the Uterus Attracts CCR10+ IgA Plasma Cells following Mucosal Vaccination via Estrogen Control

“…Differences include the commensal microbiota, IgG mainly from the circulation, and hormonal fluctuations that can modify genital immunity (4). Also, female reproductive tissues must tolerate sperm and developing fetuses and respond to sexually transmitted bacterial and viral pathogens (5). Naturally occurring Abs in uterine luminal fluid might help to protect the endometrium against microbial infections (6).…”

“…Naturally occurring Abs in uterine luminal fluid might help to protect the endometrium against microbial infections (6). Several previous studies suggested that epithelial cells in the genital tract have a key role in Ag presentation and immune responses, although there are no distinct lymphoid structures in the genital tract (5,7). It is critical to understand the female genital tract immune system to develop strategies against such sexually transmitted infections as HSV-2, Chlamydia trachomatis, human papillomavirus, and HIV (8)(9)(10)(11).…”