The schistosome glutathione S-transferase P28GST, a unique helminth protein, prevents intestinal inflammation in experimental colitis through a Th2-type response with mucosal eosinophils

Mucosal Immunol. 2016 Mar;9(2):322-35. doi: 10.1038/mi.2015.62. Epub 2015 Jul 15.

Abstract

Intestinal helminth parasites are potent inducers of T helper type 2 (Th2) response and have a regulatory role, notably on intestinal inflammation. As infection with schistosomes is unlikely to provide a reliable treatment of inflammatory bowel diseases, we have investigated the beneficial effect of a schistosome enzymatic protein, the 28-kDa glutathione S-transferase (P28GST), on the modulation of disease activity and immune responses in experimental colitis. Our results showed that immunization with recombinant P28GST is at least as efficient as established schistosome infection to reduce colitis lesions and expression of pro-inflammatory cytokines. Considering underlying mechanisms, the decrease of inflammatory parameters was associated with the polarization of the immune system toward a Th2 profile, with local and systemic increases of interleukin (IL)-13 and IL-5. Dense eosinophil infiltration was observed in the colons of P28GST-immunized rats and mice. Depletion of eosinophils by treatment with an anti-Siglec-F monoclonal antibody and use of IL-5-deficient mice led to the loss of therapeutic effect, suggesting the crucial role for eosinophils in colitis prevention by P28GST. These findings reveal that immunization with P28GST, a unique recombinant schistosome enzyme, ameliorates intestinal inflammation through eosinophil-dependent modulation of harmful type 1 responses, representing a new immuno-regulatory strategy against inflammatory bowel diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Differentiation, Myelomonocytic
  • Cell Movement
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / pathology
  • Colitis / prevention & control*
  • Colon / immunology*
  • Colon / parasitology
  • Colon / pathology
  • Disease Models, Animal
  • Eosinophils / immunology*
  • Eosinophils / parasitology
  • Eosinophils / pathology
  • Female
  • Glutathione Transferase / administration & dosage
  • Glutathione Transferase / chemistry
  • Glutathione Transferase / immunology*
  • Helminth Proteins / administration & dosage
  • Helminth Proteins / chemistry
  • Helminth Proteins / immunology*
  • Immunization
  • Interleukin-13 / biosynthesis
  • Interleukin-13 / immunology
  • Interleukin-5 / biosynthesis
  • Interleukin-5 / deficiency
  • Interleukin-5 / immunology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / parasitology
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Schistosoma mansoni / chemistry
  • Schistosoma mansoni / immunology
  • Schistosomiasis mansoni / immunology*
  • Schistosomiasis mansoni / parasitology
  • Th1 Cells / immunology
  • Th1 Cells / parasitology
  • Th1 Cells / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / parasitology
  • Th2 Cells / pathology
  • Trinitrobenzenesulfonic Acid

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, Myelomonocytic
  • Helminth Proteins
  • Interleukin-13
  • Interleukin-5
  • Recombinant Proteins
  • Siglecf protein, mouse
  • Trinitrobenzenesulfonic Acid
  • Glutathione Transferase