Innate Immunity in the Female Reproductive Tract: Role of Sex Hormones in Regulating Uterine Epithelial Cell Protection Against Pathogens

Abstract

The mucosal immune system in the upper female reproductive tract is uniquely prepared to maintain a balance between the presence of commensal bacteria, sexually transmitted bacterial and viral pathogens, allogeneic spermatozoa, and an immunologically distinct fetus. At the center of this dynamic system are the epithelial cells that line the Fallopian tubes, uterus, cervix and vagina. Epithelial cells provide a first line of defense that confers continuous protection, by providing a physical barrier as well as secretions containing bactericidal and virucidal agents. In addition to maintaining a state of ongoing protection, these cells have evolved to respond to pathogens, in part through Toll-like receptors (TLRs), to enhance innate immune protection and, when necessary, to contribute to the initiation of an adaptive immune response. Against this backdrop, epithelial cell innate and adaptive immune function is modulated to meet the constraints of procreation. The overall goal of this review is to focus on the dynamic role of epithelial cells in the upper reproductive tract, with special emphasis on the uterus, to define the unique properties of these cells as they maintain homeostasis in preparation for successful fertilization and pregnancy while at the same time confer protection against sexually transmitted infections, which threaten to compromise women's reproductive health and survival. By understanding the nature of this protection and the ways in which innate and adaptive immunity are regulated by sex hormones, these studies provide the opportunity to contribute to the foundation of information essential for ensuring reproductive health.

Medroxyprogesterone Acetate Differentially Regulates Interleukin (IL)-12 and IL-10 in a Human Ectocervical Epithelial Cell Line in a Glucocorticoid Receptor (GR)-dependent Manner

“…Epithelial cells lining the female genital tract play a protective role when this site is exposed to pathogens (27)(28)(29). In addition to providing a physical barrier against sexually transmitted pathogens, these epithelial cells are also capable of producing a wide variety of cytokines and chemokines that regulate both innate and acquired local immune responses (27)(28)(29)(30)(31). This cytokine milieu in the female genital tract is a vital determinant of inflammation (30 -32) and most likely susceptibility to infections (32)(33)(34)(35)(36)(37)(38).…”

Expression of antimicrobial peptides in the epithelium of the cervix uteri after caesarian section and vaginal birth

“…В то же время лактобациллы и при бактериоскопическом, и при бактериологическом исследовании на 3-е сутки по-слеоперационного периода выявлялись достовер-но реже, чем у пациенток, родоразрешенных через естественные родовые пути. Так как синтез аМП усиливается при увеличении бактериальной обсе-мененности [18], различия в секреции дефензинов после абдоминального и влагалищного родораз-решения могут быть обусловлены особенностями восстановления микробиоценоза половых путей. еще одной причиной, способствующей сниже-нию экспрессии антимикробных пептидов после родов через естественные родовые пути, могут быть различия в гормональном статусе пациен-ток.…”

Lactic Acid Bacteria in the Prevention of Urogenital and Respiratory Infections

“…The immune system represents an important component of the reproductive tract (Wira et al 2005a ;Witkin et al 2007 ; Barrons and Tassone 2008 ;Ochiel et al 2008 ) infl uencing many of the biological functions of the host. The regulation of the immune response of the UGT is very complex because this mucosal surface must deal with members of the indigenous microbiota, many potential pathogens, spermatozoa, and the fetus.…”

“…The UGT mucosal immune system and the systemic immune system are similar in the protection against potential pathogens, which is provided by innate (fi rst line of defense) and adaptive immunity (Wira et al 2005a(Wira et al , 2005bWitkin et al 2007 ;Barrons and Tassone 2008 ;Ochiel et al 2008 ). An effective specifi c immune response against pathogens requires the antigen process by the Antigen -Presenting Cells, and the protection is achieved through humoral immunity (specifi c antibodies produced by B cells) or cell -mediated immunity (direct or indirect destruction of pathogens by T cells).…”