Pattern Recognition via the Toll-Like Receptor System in the Human Female Genital Tract

Abstract

The mucosal surface of the female genital tract is a complex biosystem, which provides a barrier against the outside world and participates in both innate and acquired immune defense systems. This mucosal compartment has adapted to a dynamic, non-sterile environment challenged by a variety of antigenic/inflammatory stimuli associated with sexual intercourse and endogenous vaginal microbiota. Rapid innate immune defenses against microbial infection usually involve the recognition of invading pathogens by specific pattern-recognition receptors recently attributed to the family of Toll-like receptors (TLRs). TLRs recognize conserved pathogen-associated molecular patterns (PAMPs) synthesized by microorganisms including bacteria, fungi, parasites, and viruses as well as endogenous ligands associated with cell damage. Members of the TLR family, which includes 10 human TLRs identified to date, recognize distinct PAMPs produced by various bacterial, fungal, and viral pathogens. The available literature regarding the innate immune system of the female genital tract during human reproductive processes was reviewed in order to identify studies specifically related to the expression and function of TLRs under normal as well as pathological conditions. Increased understanding of these molecules may provide insight into site-specific immunoregulatory mechanisms in the female reproductive tract.

The role of pattern recognition receptors in the innate recognition ofCandida albicans

“…40,42,43 The activation of MyD88 and TRIF lead to MyD88-dependent pathway and the MyD88-independent (TRIF-dependent) pathway respectively. 44 In contrast, CLRs are mostly associated with the spleen tyrosine kinase (SYK) (Fig. 1), which activates MAPK (mitogen-activated protein kinase).…”

CD300F Blocks Both MyD88 and TRIF-Mediated TLR Signaling through Activation of Src Homology Region 2 Domain-Containing Phosphatase 1

“…TLR9 interacts with unmethylated deoxytidyl-phosphate-deoxyguanosine (CpG) motifs commonly found in bacterial and viral DNA, whereas TLR3 recognizes dsRNA from viral origins (reviewed in Ref. 12). Two main pathways mediate TLR4-induced signaling: one is mediated by a complex containing MyD88 and Toll/IL-1R domaincontaining adaptor protein (TIRAP), and the other is mediated by a TRIF and TRIF-related adaptor molecule (TRAM) complex.…”

Profiles and technological requirements of urogenital probiotics

“…The mucosal components of the lower genital tracts have adapted to a dynamic, nonsterile environment challenged by a variety of antigenic/inflammatory stimuli associated with sexual intercourse and endogenous vaginal microbiota [184,187]. Clearly, it is essential that these mucosal tissues develop mechanisms for selectively respond to pathogens, while simultaneously avoid chronic inflammation due to immune responses to commensal microorganisms.…”

“…The innate immune system in the female genital tract is highly complex and multifactorial. Mucosal epithelial cells, fibroblasts, lymphocytes, macrophages and dendritic cells associated with the female genital tract have evolved a unique mechanism for the recognition of pathogens [187]. These cells express a variety of Toll-like receptors (TLRs), allowing them to recognize the different repertoire of a wide range of molecular patterns associated with pathogens (PAMPs) [187,188].…”

“…Mucosal epithelial cells, fibroblasts, lymphocytes, macrophages and dendritic cells associated with the female genital tract have evolved a unique mechanism for the recognition of pathogens [187]. These cells express a variety of Toll-like receptors (TLRs), allowing them to recognize the different repertoire of a wide range of molecular patterns associated with pathogens (PAMPs) [187,188]. TLRs recognize conserved PAMPs synthesized by microorganisms including bacteria, fungi, parasites, and viruses as well as endogenous ligands associated with cell damage.…”