The Effects of Intestinal Nematode L4 Stage on Mouse Experimental Autoimmune Encephalomyelitis

Arch Immunol Ther Exp (Warsz). 2018 Jun;66(3):231-243. doi: 10.1007/s00005-017-0489-z. Epub 2017 Oct 3.

Abstract

Helminths use various immunomodulatory and anti-inflammatory strategies to evade immune attack by the host. During pathological conditions, these strategies alter the course of disease by reducing immune-mediated pathology. The study examines the therapeutic effect of the nematode L4 stage based on an in vivo model of multiple sclerosis, monophasic encephalomyelitis (EAE), induced by sensitization with MOG35-55 peptide in C57BL/6 female mice infected with the intestinal nematode Heligmosomoides polygyrus. The EAE remission was correlated with altered leukocyte number identified in the central nervous system (CNS), and temporary permeability of the blood-brain barrier at the histotrophic phase of infection. At 6 days post-infection, when the L4 stage had almost completely attenuated the clinical severity and pathological signs of EAE, CD25+ cell numbers expanded significantly, with parallel growth of CD8+ and CD4+, both CD25+Foxp3+ and CD25+Foxp3- subsets and alternatively activated macrophages. The phenotypic changes in distinct subsets of cerebrospinal fluid cells were correlated with an inhibited proliferative response of encephalitogenic T cells and elevated levels of nerve growth factor and TGF-β. These results enhance our understanding of mechanisms involved in the inhibition of immune responses in the CNS during nematode infection.

Keywords: EAE; Helminth therapy; Immunomodulation; Nematodes.

MeSH terms

  • Animals
  • Blood-Brain Barrier
  • Central Nervous System / immunology*
  • Central Nervous System / parasitology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / parasitology
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunomodulation
  • Intestines / immunology*
  • Intestines / parasitology
  • Life Cycle Stages
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / parasitology
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Nematospiroides dubius / physiology*
  • Nerve Growth Factor / metabolism
  • Peptide Fragments / immunology
  • Strongylida Infections / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / metabolism

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Transforming Growth Factor beta
  • myelin oligodendrocyte glycoprotein (35-55)
  • Nerve Growth Factor