NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION AND GUT MICROBIOTA MODULATION

Abstract

ntroduction: Recent studies implicated overactivated myeloid cells and gut microbiome, along with our work, in multiple sclerosis (MS) pathogenesis. As we have shown before, prostaglandin (PG)E2 promotes suppressive properties of myeloid cells leading to amelioration of symptoms in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). Additionally, we investigated how the changes of gut microbiota associate with EAE and the effects of therapy. Materials & Methods: MOG35-55 in Complete Freund Adjuvans was used for EAE induction in C57BL/6 mice. Gold nanoparticles (GNP) conjugated with PGE2 and MOG were applied on the day 1, 3, 5, 7, and 9 post-immunization. We performed extensive immunophenotyping and metagenomic analysis in order to decipher association between gut microbiome and efficacy of GNP-MOG-PGE2 treatment. Results: GNP-MOG-PGE2 treatment alleviates EAE symptoms, decreased levels of pro-inflammatory cytokines in sera, and increased proportion of suppressive MDSCs in CNS-infiltrates. Furthermore, EAE induction significantly affected species richness, while GNP-MOG-PGE2 treatment increased the gut microbiota diversity and preserved the richness of species with immunomodulatory properties. Conclusion: Taken together, our data indicate that targeted activation of myeloid cells by GNP-MOG-PGE2 together with gut microbiota modification is very promising therapeutic strategy for MS.