Marilen Benner

MICROBIOTA AND ENDOMETRIAL HEALTH 159 6 Pattern recognition receptors To detect viral, fungal and bacterial pathogens, the innate immune system senses pathogen- associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs), such as toll-like receptors (TLRs), RIG-I-like receptors, NOD-like receptors (NLRs) and C-type lectin receptors, such as collectins, selectins, endocytic receptors and proteoglycans (151-153). PAMPs include, for example, cell wall mannans (yeast), formylated or lipo-peptides, peptidoglycans, teichoic acids and bacterial cell-wall components such as LPS (154). Activation of TLR induces Nuclear factor-kappa B (NF к B), which initiates an inflammatory cascade including upregulation of markers to mount an adaptive immune response (155). PRRs form the first line of defense against sexually transmitted disease or any other pathogens that can access the female reproductive tract through the vagina (156). For example, decidual and uterine stromal and epithelial cells express various TLRs and other PRRs, and the cells mount a potent inflammatory response upon receptor recognition (157-162). An overview of TLRs of the endometrium is given in Table II. The expression of TLR mRNA and protein changes throughout the menstrual cycle, as shown by different groups (163-167). Receptor expression on endometrial cells was found to be low in the proliferative phase and increased in the secretory phase for TLRs 1 – 10. Together with intracellular receptors, there is a constitutively high expression of pathogenicity sensors lining the female reproductive tract (160). All of these receptors can sense their specific PAMP and react by inducing signaling cascades. Evidence accumulates that PRRs are one way for microbiota and host to communicate. Round and colleagues examined how B. fragilis induces symbiosis via TLR2 of CD4 + T cells. PSA of B. fragilis induces Foxp3 + regulatory cells that are needed to counteract the otherwise Th17- mediated killing of Bacteroides (168). Nod2 -deficient mice were more susceptible to pathogenic infection (169). Nod2 was shown to control dysregulated commensal colonization, and commensal resident bacteria are in turn needed to induce Nod2 expression. TLRs and NLRs are suspected to play a role in the periconceptual regulation as they are major players in the cascade of cytokine induction (86, 170). Protection against pathogens Maintaining colonization of commensal bacteria protects the host against pathogens. Residential microbiota successfully compete for the niche by exhibiting better adaptation than an occasionally invading pathogenic species, termed the “colonization resistance” concept (171, 172). Commensal microbiota are specialized in nutrient usage of their habitat, and deplete the environment of nutrients needed for pathogenic species. Consumption of a limited resource can starve the pathogenic invader (173). E. coli, for example, competes in consumption of sugars, amino acids and other nutrients with the pathogenic enterohaemorrhagic E. coli (EHEC) (174, 175). Symbionts also defend their niche (176). An example is the commensal Clostridium scindens whose colonization protects against C. difficile infection by production of secondary