title: Combination of worm antigen and proinsulin prevents type 1 diabetes in NOD mice after the onset of insulitis.
abstract: Animal studies demonstrated that administration of helminth products can protect from autoimmune diseases. However, the success of such administrations is limited in the case of type 1 diabetes, as protection is only provided if the administration is started before the development of insulitis. In this study we investigated whether inclusion of helminth antigen administrations to an antigen-specific treatment with proinsulin improves the protective effect by triggering non-specific regulatory immune responses. Using a combination therapy of intraperitoneal Litomosoides sigmodontis antigen and intranasal pro-insulin, onset of diabetes was prevented in NOD mice after insulitis started, while either administration alone failed to protect. This protection was associated with an increased frequency of regulatory T cells within the pancreatic lymph nodes and a reduced inflammation of the pancreatic islets. This suggests that inclusion of helminth antigens improve the protective effect provided by antigen-specific therapies and represent a new potential therapeutic approach against autoimmune diseases.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Germany.
authors.forename: Jesuthas
authors.initials: J
authors.lastname: Ajendra
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Germany; Department of Microbiology and Parasitology, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
authors.forename: Afiat
authors.initials: A
authors.lastname: Berbudi
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Germany; German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Germany. Electronic address: huebner@microbiology-bonn.de.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Hübner
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000947:Antigens, Helminth / Q000494:pharmacology / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005370:Filarioidea / Q000276:immunology*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D016688:Mice, Inbred NOD; D011384:Proinsulin / Q000494:pharmacology / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D000947:Antigens, Helminth; D007328:Insulin; D011384:Proinsulin
keywords: Filariae; Helminth; Litomosoides sigmodontis; Proinsulin; Regulatory T cells; Type 1 diabetes