Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization.
Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS) characterized by chronic inflammatory demyelination of the central nervous system (CNS). The pathology of EAE involves autoimmune CD4(+) T(h)1 cells. There is a striking inverse correlation between the occurrence of parasitic and autoimmune diseases. We demonstrate that in mice with Schistosoma mansoni ova immunization, the severity of EAE is reduced as measured by decreased clinical scores and CNS cellular infiltrates. Disease suppression is associated with immune deviation in the periphery and the CNS, demonstrated by decreased IFN-gamma and increased IL-4, transforming growth factor-beta and IL-10 levels in the periphery, and increased frequency of IL-4 producing neuroantigen-specific T cells in the brain. S. mansoni helminth ova treatment influenced the course of EAE in wild-type mice, but not in STAT6-deficient animals. This indicates that STAT6 plays a critical role in regulating the ameliorating effect of S. mansoni ova treatment on the autoimmune response, and provides the direct link between helminth treatment, T(h)2 environment and improved EAE. As some intestinal helminthic infections induce minimal pathology, they might offer a safe and inexpensive therapy to prevent and/or ameliorate MS.
Sewell
Diane
D
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA.
Qing
Zhu
Z
Reinke
Emily
E
Elliot
David
D
Weinstock
Joel
J
Sandor
Matyas
M
Fabry
Zsuzsa
Z
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006376:Helminths; D007114:Immunization; D015847:Interleukin-4 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009103:Multiple Sclerosis / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology*; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000172:deficiency
D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D010047:Ovalbumin