Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, Which Promote Eosinophilia

J Immunol. 2016 Jan 15;196(2):703-14. doi: 10.4049/jimmunol.1501820. Epub 2015 Dec 16.


Epidemiologic studies in humans have demonstrated that infection with helminth parasites is associated with a reduced risk of developing autoimmune diseases. Mechanistic studies in mice have linked the protective effect of helminths on autoimmunity to the suppressive activity of helminth-induced regulatory T cells (Tregs) or Th2 cells. In this study, we demonstrate that treatment of mice with Fasciola hepatica excretory-secretory products (FHES) attenuated the clinical signs of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Protection was associated with a significant reduction in the infiltration of pathogenic Th1 and Th17 cells into the brain. Although FHES enhanced anti-inflammatory cytokine and Th2 responses, protection against EAE was independent of IL-4, IL-10, and Tregs. However, administration of FHES induced production of the type 2 cytokines IL-33 and IL-5, which promoted accumulation of eosinophils. FHES-induced expansion of eosinophils and protection against EAE was lost in IL-33(-/-) mice and upon neutralization of IL-5. Furthermore, transfer of FHES-induced or IL-33-induced eosinophils conferred protection against EAE. In addition, treatment of mice with recombinant IL-33 attenuated autoimmunity, and this was dependent on IL-5. To our knowledge, this study is the first to report a role for helminth-induced IL-5 and IL-33 in protection against autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology*
  • Autoimmunity / immunology*
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / microbiology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Eosinophilia / immunology*
  • Flow Cytometry
  • Immunity, Innate / immunology
  • Interleukin-33 / immunology*
  • Interleukin-5 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Th2 Cells / immunology*


  • Antigens, Helminth
  • Il33 protein, mouse
  • Interleukin-33
  • Interleukin-5