title: M cell targeting with Aleuria aurantia lectin as a novel approach for oral allergen immunotherapy.
abstract: BACKGROUND
  The extent and quality of the immune response to orally applied allergens may critically depend on the precise site of uptake at the intestinal mucosa.
  
  
  OBJECTIVE
  The aim of this study was to construct allergen vehicles optimized for oral allergen immunotherapy.
  
  
  METHODS
  By using a murine model, we examined the immunomodulatory effect of birch pollen proteins entrapped in poly(D,L-lactide-co-glycolide) microspheres, which were specifically targeted to enterocytes or to M cells, in an ongoing T h 2 response. BALB/c mice express different carbohydrates on these 2 cell types. To target the sialylic residues on murine enterocytes, we functionalized microspheres with wheat germ agglutinin (WGA) and, to target alpha-L-fucose on M cells, with a lectin from Aleuria aurantia (AAL), the orange peel mushroom.
  
  
  RESULTS
  Both WGA and AAL functionalization enhanced binding to human Caco2 cells substantially, which express sialylic and, as carcinoma cells, also alpha-L-fucose residues. Different groups of BALB/c mice were first sensitized to birch pollen and subsequently fed with birch pollen-loaded functionalized (WGA microspheres, AAL microspheres) or nonfunctionalized, birch pollen extract-loaded particles. When mice were fed with AAL microspheres, birch pollen-specific IgG2a, but not IgG1 or IgE, increased significantly. As expected, in a 3 H-thymidin assay, their splenocytes proliferated specifically on birch pollen stimulation. Both targeting strategies, using WGA or AAL, induced IL-10 as well as IL-4 production. However, in AAL microsphere-treated mice, IFN-gamma synthesis was significantly increased, which may be responsible for the significant IgG2a production in this group.
  
  
  CONCLUSIONS
  Our data indicate that targeting M cells by using AAL-coated allergen vehicles may be a promising strategy for oral allergen immunotherapy.
authors.affiliation: Department of Pathophysiology, Medical University of Vienna, Austria.
authors.forename: Franziska
authors.initials: F
authors.lastname: Roth-Walter
authors.forename: Isabella
authors.initials: I
authors.lastname: Schöll
authors.forename: Eva
authors.initials: E
authors.lastname: Untersmayr
authors.forename: Renate
authors.initials: R
authors.lastname: Fuchs
authors.forename: George
authors.initials: G
authors.lastname: Boltz-Nitulescu
authors.forename: Andrea
authors.initials: A
authors.lastname: Weissenböck
authors.forename: Otto
authors.initials: O
authors.lastname: Scheiner
authors.forename: Franz
authors.initials: F
authors.lastname: Gabor
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D003888:Desensitization, Immunologic / Q000379:methods*; D020895:Enterocytes / Q000187:drug effects*; D005260:Female; D006016:Glycolates / Q000008:administration & dosage; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D019344:Lactic Acid; D037102:Lectins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D006016:Glycolates; D007074:Immunoglobulin G; D037102:Lectins; C064549:lectin, Aleuria aurantia; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma