title: Worm proteins of Schistosoma mansoni reduce the severity of experimental chronic colitis in mice by suppressing colonic proinflammatory immune responses.
abstract: Although helminthic therapy as a possible new option to treat inflammatory bowel disease is a well-established concept by now, the search for immunomodulatory helminth-derived compounds and their mechanisms of action is still ongoing. We investigated the therapeutic potential and the underlying immunological mechanisms of Schistosoma mansoni soluble worm proteins (SmSWP) in an adoptive T cell transfer mouse model of chronic colitis. Both a curative and a preventive treatment protocol were included in this study. The curative administration of SmSWP (started when colitis was established), resulted in a significant improvement of the clinical disease score, colonoscopy, macroscopic and microscopic inflammation score, colon length and myeloperoxidase activity. The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score. Both the curative and preventive SmSWP treatment downregulated the mRNA expression of the proinflammatory cytokines IFN-γ and IL-17A and upregulated the mRNA expression of the anti-inflammatory cytokine IL-4 in the colon at the end of the experiment. This colonic immunomodulatory effect of SmSWP could not be confirmed at the protein level. Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment. In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon.
authors.affiliation: Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
authors.forename: Marthe
authors.initials: M
authors.lastname: Heylen
authors.affiliation: Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
authors.forename: Nathalie E
authors.initials: NE
authors.lastname: Ruyssers
authors.affiliation: Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
authors.forename: Joris G
authors.initials: JG
authors.lastname: De Man
authors.affiliation: Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Timmermans
authors.affiliation: Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium; Antwerp University Hospital, Division of Gastroenterology & Hepatology, Antwerp, Belgium.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Pelckmans
authors.affiliation: Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium; Antwerp University Hospital, Division of Gastroenterology & Hepatology, Antwerp, Belgium.
authors.forename: Tom G
authors.initials: TG
authors.lastname: Moreels
authors.affiliation: Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
authors.forename: Benedicte Y
authors.initials: BY
authors.lastname: De Winter
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015801:Helminth Proteins / Q000008:administration & dosage*; D007378:Interleukins / Q000097:blood / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D012550:Schistosoma mansoni / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015801:Helminth Proteins; D007378:Interleukins