title: Therapeutic potential of larval excretory/secretory proteins of the pig whipworm Trichuris suis in allergic disease.
abstract: BACKGROUND
  Gastrointestinal nematodes are currently being evaluated as a novel therapeutic in the treatment of chronic human inflammatory disorders, due to their unique ability to induce immunoregulatory pathways in their hosts. In particular, administration of ova from the pig whipworm Trichuris suis (T. suis; TSO) has been proposed for the treatment of allergic, inflammatory and autoimmune disorders. Despite these advances, the biological pathways through which TSO therapy modulates the host immune system in the context of human disease remain undefined.
  
  
  METHODS
  We characterized the dominant proteins present in the excretory/secretory (E/S) products of first-stage (L1) T. suis larvae (Ts E/S) using LC-MS/MS analysis and examined the immunosuppressive properties of whole larval Ts E/S in vitro and in a murine model of allergic airway disease.
  
  
  RESULTS
  Administration of larval Ts E/S proteins in vivo during the allergen sensitization phase was sufficient to suppress airway hyperreactivity, bronchiolar inflammatory infiltrate and allergen-specific IgE production. Three proteins in larval Ts E/S were unambiguously identified. The immunomodulatory function of larval Ts E/S was found to be partially dependent on the immunoregulatory cytokine IL-10.
  
  
  CONCLUSIONS
  Taken together, these data demonstrate that the released proteins of larval T. suis have significant immunomodulatory capacities and efficiently dampen allergic airway hyperreactivity. Thus, the therapeutic potential of defined larval E/S proteins should be exploited for the treatment of human allergic disorders.
authors: Institute of Immunology, Freie Universität Berlin, Berlin, Germany.
authors: F
authors: F
authors: Ebner
authors: M R
authors: MR
authors: Hepworth
authors: S
authors: S
authors: Rausch
authors: K
authors: K
authors: Janek
authors: A
authors: A
authors: Niewienda
authors: A
authors: A
authors: Kühl
authors: P
authors: P
authors: Henklein
authors: R
authors: R
authors: Lucius
authors: E
authors: E
authors: Hamelmann
authors: S
authors: S
authors: Hartmann
mesh_terms: D000485:Allergens / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D056747:Immunomodulation; D016753:Interleukin-10 / Q000378:metabolism; D007814:Larva / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013552:Swine; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D061147:Therapy with Helminths; D014258:Trichuris / Q000276:immunology*
chemical_list: D000485:Allergens; D000947:Antigens, Helminth; D016207:Cytokines; D010455:Peptides; D016753:Interleukin-10
keywords: Trichuris suis; asthma; excretory/secretory proteins; helminth therapy; immunomodulation