Unique features of antiviral immune system of the vaginal mucosa

Abstract

A vast majority of human vaccines rely on neutralizing antibodies for protection. With the exception of vaccines against human papillomavirus, despite a great amount of dedicated effort by the scientific community, development of vaccines against sexually transmitted viruses has generally been unsuccessful. Understanding the immunobiology of the genital tract is key to designing vaccines that prevent spreading of these viruses. Recent studies demonstrate that adaptive immunity in the vaginal mucosa is uniquely regulated compared to other mucosal organs. In particular, development of virus-specific CD4+ and CD8+ T cells is critically important for antiviral defense in vagina. In this review, we provide an overview of our current understanding of a wide spectrum of immune responses in vagina--from innate viral sensing to memory development.

Figure 1. Antiviral adaptive immune responses in the cervical and vaginal mucosa

Viral exposure is often thought to occur through the transformation zone or through microabrasion. At steady state, vaginal epithelial layer and the submucosa are surveyed by innate leukocytes and lymphocytes, but the recruitment of antigen-specific T and B cells to the vagina is restricted. Once infected, both epithelial cells and innate leukocytes produce type I IFNs, inflammatory cytokines and induce chemokines that recruit NK cells, monocytes, pDCs and neutrophils. Virions and viral antigens are taken up and processed by migrant submucosal DCs or by LN-resident DCs and presented to T cells. Activated effector T cells are recruited to the vagina and can persist for a long period. Vaginal epithelial cells lack polymeric Ig receptor (pIgR) for transport of sIgA. Instead, virus-specific IgG is transcytosed by FcRn into the vaginal lumen, and provides protection.