Marilen Benner

CHAPTER 6 158 chemoattractant protein 1 involved in directing monocytes, T cells and DCs to inflammatory or tumor tissue (138) (139, 140). Also, decidual stromal cells obtained during first trimester (~8 weeks in both studies) secrete CCL2, which was shown to attract Th2 and Th17 cells, thereby influencing the local T cell balance (141, 142). In addition, macrophage recruitment and polarization (143), and plasmacytoid DCs were affected by CCL2. It was recently shown that microbiota are important in establishing baseline CCL2 secretion controlling homeostatic trafficking of plasmacytoid DCs (144). As no functional contribution of endometrial microbiota has been shown yet, the physiologically closest possible microbiome, as indicated by Chen et al. (2017), is probably the cervicovaginal microbiome. Cytokine concentrations were shown to be affected depending on the microbial profiles of 16S rRNA analysis of cervicovaginal lavage. This was reflected in lower IL-1beta, IL-8 and IL-10 levels in bacterial vaginosis (BV) (145). Also other cytokines, such as LIF, GM-CSF, colony-stimulating factor-1, heparin binding EGF like growth factor, insulin-like growth factor Iand II, contribute to fertility through their role in supporting blastocyst development in the pre-implantation phase (87). Decreased LIF expression of endometrial epithelial cells was shown to be associated with infertility (146). Cervicovaginal levels of cytokines were affected by the bacterial flora found (147) and a probiotic supplement was shown to affect vaginal interleukin changes (148). It remains to be seen if different uterine microbial profiles could be associated with altered chemokine/cytokine profiles and effects on reproductive success. LESSONS LEARNED FROM THE GUT MICROBIOME: POSSIBLE INTERACTIONS BETWEEN LOCAL MICROBIOME AND ENDOMETRIUM Besides influence on systemic and tissue resident lymphocytes, the microbiota and host interact on various levels. The relation between microbes and host is not a black and white phenomenon; and thus surpasses the simplified view of commensal versus pathogen. The immune system shapes a homeostatic co-existence, i.e. by eliminating species that might not only be harmful but also disturb the balance (12). Two different types of battles are continuously fought when hosting a microbial community: one that is responsible for facing the daily challenge posed by containment of symbiotic microbes, and one for defense against pathogenic microbes that breach containment (12, 149). Although our understanding of the microbiome – host interaction is still rudimentary, its functional importance, especially on various arms of innate and adaptive immunity, is evident (7, 150). Below, we give an overview of the different mechanisms of how endometrial colonization might have implications for the uterine immune-environment, and thus for fertility.