Mapping the immunological receptors CD14 and macrophage receptor with collagenous structure (MARCO) and their innate recognition potential on trophoblast cells: relevance for human pregnancy

The feto-maternal interface is vital to promote growth and development of the placenta while maintaining tolerance and surveillance through the immune system. Pathogens are detected through pattern recognition receptors, which have a key role in the innate recognition by transducing signals from pathogen-associated molecular patterns. Lipopolysaccharide, a PAMP of Gram-negative bacterium, is recognized by the Toll-like receptor. Cluster of differentiation (CD) 14 and macrophage receptor with collagenous structure (MARCO) are key players in innate recognition. The hypothesis derived from the above is that MARCO might be expressed on trophoblast cells and plays a valuable role in association with CD14. The interaction of CD14 and MARCO was explored with the use of confocal microscopy which showed physical associations, most likely contributing to their function at the feto-maternal interface. Trophoblast responses to LPS indicated a significant role in regulating the expression of CD14 and MARCO and NF-κB translocation and activation. It was also hypothesized a correlation between the down-regulation of Myoferlin and vascular endothelial growth factor (VEGF), and the decreased cell proliferation of trophoblast cells upon treatment with LPS. Myoferlin and VEGF quantification estimated by flow cytometry and western blotting showed significant decrease in LPS treated JEG-3 cells in time and dose dependent manner. The cell proliferation assay revealed a significant decrease in trophoblast cell growth of LPS treatment suggesting it is associated with the decrease of Myoferlin of which the expression is reported to be correlated with VEGF. These data suggest that CD14 and MARCO can be modulated and thus might contribute to feto-maternal tolerance and surveillance preventing pregnancy complications such as preeclampsia.