Systemic microbial antigen administration ameliorates experimental autoimmune encephalomyelitis via MHC-II downregulation in the CNS and secondary lymphoid organs.

Abstract

Microbial stimuli modulate CNS neuroinflammation but the exact molecular mechanisms are largely unknown. In this study, we aimed to delineate the effect of systemic pre-disease microbial antigen administration of 2 different microbial strains on systemic and CNS immune responses in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in wtC57/BL5 mice. The mice received either Helicobacter pylori (Hp) or E coli antigen or PBS by 3 weekly intraperitoneal injections prior to EAE induction. Mice subjected to microbial antigen administration displayed decreased disease incidence and severity compared to controls. These results were linked with reduced splenocyte proliferation against MOG peptide in vitro and decreased expression of chemoattractant chemokines in both peripheral lymphoid organs and the CNS compared to controls. EAE amelioration was associated with a relative increase in Iba1+ arginase+ anti-inflammatory microglia in the CNS and with reduced MHC-II expression levels in antigen-presenting cells, indicated by reduction of Tmem+MHC-II+ microglia and Ly6C+MHC-II+ monocyte-derived macrophages. Our data provide mechanistic insight into the immune tolerance induced via systemic administration of 2 different microbial strain antigens in the context of CNS autoimmunity, possibly via the modulation of antigen-presentation via non-myelin peptide-specific mechanisms.