title: The schistosome glutathione S-transferase P28GST, a unique helminth protein, prevents intestinal inflammation in experimental colitis through a Th2-type response with mucosal eosinophils.
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.
authors.affiliation: Université de Lille, Inserm U995, Lille, France.
authors.forename: V
authors.initials: V
authors.lastname: Driss
authors.affiliation: Université de Lille, Inserm U995, Lille, France.|Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: El Nady
authors.affiliation: Université de Lille, Inserm U995, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Delbeke
authors.affiliation: Intestinal Biotech Development, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Rousseaux
authors.affiliation: Intestinal Biotech Development, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Dubuquoy
authors.affiliation: Université de Lille, Inserm U995, Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Sarazin
authors.affiliation: Université de Lille, Inserm U995, Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Gatault
authors.affiliation: Université de Lille, Inserm U995, Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Dendooven
authors.affiliation: Université de Lille, Inserm U1019-CNRS UMR 8204, Institut Pasteur de Lille, Lille, France.
authors.forename: G
authors.initials: G
authors.lastname: Riveau
authors.affiliation: Gastroenterology Department, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Université de Lille, Inserm U995, Lille, France.|Service des Maladies de L'Appareil Digestif et de la Nutrition, CHRU Lille, Lille, France.
authors.forename: P
authors.initials: P
authors.lastname: Desreumaux
authors.affiliation: Université de Lille, Inserm U995, Lille, France.
authors.forename: L
authors.initials: L
authors.lastname: Dubuquoy
authors.affiliation: Université de Lille, Inserm U995, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Capron
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015214:Antigens, Differentiation, Myelomonocytic; D002465:Cell Movement; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D005260:Female; D005982:Glutathione Transferase / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D015801:Helminth Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007114:Immunization; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D012550:Schistosoma mansoni / Q000737:chemistry / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D018417:Th1 Cells / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000911:Antibodies, Monoclonal; D015214:Antigens, Differentiation, Myelomonocytic; D015801:Helminth Proteins; D018793:Interleukin-13; D015848:Interleukin-5; D011994:Recombinant Proteins; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C443130:Siglecf protein, mouse; D014302:Trinitrobenzenesulfonic Acid; D005982:Glutathione Transferase