Systemic microbial antigen administration ameliorates experimental autoimmune encephalomyelitis via MHC-II

Marina Boziki1, Paschalis Theotokis1, Evangelia Kesidou1

  • 1Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Insights

Administering microbial antigens from Helicobacter pylori or E. coli before disease onset reduced the incidence and severity of experimental autoimmune encephalomyelitis (EAE). This immune tolerance involved modulating antigen presentation and increasing anti-inflammatory microglia in the central nervous system (CNS).

Area of Science:

  • Neuroimmunology
  • Microbial Immunology
  • Autoimmunity

Background:

  • Microbial stimuli influence central nervous system (CNS) neuroinflammation, but underlying molecular mechanisms remain unclear.
  • Understanding how microbial antigens affect CNS autoimmunity is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the impact of systemic pre-disease microbial antigen administration on immune responses in a mouse model of CNS autoimmunity.
  • To elucidate the molecular mechanisms by which microbial antigens induce immune tolerance in experimental autoimmune encephalomyelitis (EAE).

Main Methods:

  • Mice were administered antigens from Helicobacter pylori (Hp) or E. coli, or PBS, via intraperitoneal injections before induction of MOG-induced EAE.
  • Evaluated disease incidence and severity, splenocyte proliferation against MOG peptide in vitro, chemokine expression in lymphoid organs and CNS, and microglia/macrophage phenotypes (Iba1, arginase, MHC-II).

Main Results:

  • Microbial antigen administration significantly decreased EAE incidence and severity compared to controls.
  • Reduced splenocyte proliferation and decreased expression of chemoattractant chemokines in both peripheral and CNS tissues were observed.
  • EAE amelioration correlated with increased anti-inflammatory microglia (Iba1+ arginase+) and reduced MHC-II expression on antigen-presenting cells in the CNS.

Conclusions:

  • Systemic administration of microbial antigens can induce immune tolerance in the context of CNS autoimmunity.
  • Mechanisms may involve modulation of antigen presentation through non-myelin peptide-specific pathways.
  • Findings offer insights into potential therapeutic interventions for neuroinflammatory diseases.