Innate immune defense against microbial invasion and infection in the genitourinary mucosa relies mainly on the epithelial lining, as in other mucosal barriers. The terminal male urethra is lined by stratified squamous epithelium, and in both males and females, the proximal urethra, urinary bladder, ureters, and renal pelvis are lined by urothelium, which is a three-layered stratified epithelium that includes a superficial single layer of umbrella cells, an intermediate layer several cells thick, and a single-cell basal cell layer. The bladder lining represents the largest surface area in the urinary tract that must protect against microbial infection and invasion. The urothelium provides a variety of innate defenses against infection, including physical barrier properties of apical uroplakin plaques, and a mucus coat. Urothelial cells produce several antimicrobial peptides, including REGIIIγ, pentraxin 3, and cathelicidin. Uromodulin, an abundant urinary protein secreted by the kidney, blocks E. coli adhesion to urothelium by binding to the bacterial pili. The innate cellular response to infection in the urinary tract is largely mediated by neutrophils. TLR4 and TLR2 expressed by umbrella cells detect PAMPs in the urinary space and signals the cells to produce chemokines and cytokines that recruit blood neutrophils and monocytes into the lamina propria, and these cells migrate through the urothelial layers into the urinary space. In severe and chronic infections, with microbial invasion through the urothelium, other innate cellular responses occur, involving ILCs, γδ T cells, NK cells, and macrophages. Despite these innate defenses, urinary tract bacterial infections, most often in females by uropathogenic E. coli, are a very common and often serious medical problem. These serious infections usually occur when urinary tract function or innate immunity is impaired.
The genital tract is protected by innate and adaptive immune mechanisms. Vaginal mucosa is lined by stratified squamous epithelium, which provides a physical barrier to infection. Langerhans cells, and a variety of DCs and macrophages have been described beneath the epithelium in the vagina and endocervix. There are also resident B and T cells in the genital mucosa. The adaptive immune system in the genitourinary mucosa lacks prominent MALTs. Unlike other mucosa, in which IgA is the dominant antibody isotype, most of the antibodies in genital secretions is IgG, about half of which is produced by plasma cells in genital tract mucosa and the rest is from the circulation. Infections in the genital tract are a major cause of morbidity and mortality worldwide and occur when the epithelial barriers are damaged or microbes evade the local mechanisms of defense.
