P755 Treponema pallidum stimulated macrophage-derived exosomal mir-146a-5p decreased monocyte transendothelial migration

Background Exosomes are small vesicles containing a wide range of functional proteins, DNA and RNA. Exosomal RNAs have been implicated in many exosome-mediated biological functions. These cell-derived Exosomes contain numerous miRNAs, which can work locally or can enter the circulation to act at distal sites. Accumulating evidences indicate that exosomal miRNA is linked to the host immune response to infection. In this study, we focused on how Treponema pallidum evade immune clearance via exosome-mediated transfer of microRNAs. Methods We first performed a comprehensive miRNA profiling in exosomes using microarray analysis. Thereafter, RT-PCR was performed to validate the expression of miR-146a-5p in exosome derived from macrophage stimulated by Treponema pallidum and syphilis patients. Laser confocal microscopy was used to trace exosomal miR-146a-5p secreted by macrophage into HUVECs. The effect of exosomal miR-146a-5p on monocytes cells transendothelial migration of HUVEC by using migration assay. Luciferase reporter assay were utilized to confirm the binding of exosomal miR-146a-5p to the 3’untranslated region of JAM-C. Results MicroRNA array was performed and 65 miRNAs were identified. Among the identified miRNAs, miR-146a-5p was one of the most significantly changed miRNAs which high expression in Treponema pallidum derived exosomes. We also confirmed that miR-146a-5p was enriched in serum exosomes of syphilis patients. Exosomal miR-146a-5p of macrophages could be transferred into HUVEC and reduce monocyte transendothelial migration by directly targeting the promoter of JAM-C. Conclusion Our date show that exosomes derived from macrophage stimulated by Treponema pallidum expressed high levels of miR-146a-5p which could be delivered to endothelial cells, and decreases monocyte transendothelial migration by targeting JAM-C in endothelial cells, which may enable Treponema pallidum evade the host immune clearance. Disclosure No significant relationships.