title: rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant.
abstract: Lactobacilli are able to induce upregulation of co-stimulatory molecules in DCs with Th1 cytokines production and increase in Treg activity. This could explain the observed effectiveness of the prolonged administration of lactobacilli in the prevention of allergic disorders in infants and envisage the possible use of bacteria expressing the allergen for the specific immunotherapy of allergic diseases. Hence, we evaluated Streptococcus thermophilus (ST) expressing rBet v 1 as allergen delivery tool and adjuvant factor for immunotherapy in Betv1-sensitized mice. rBet v 1 gene was introduced and expressed in ST (ST[rBet v 1]). BALB/c mice were sensitized with rBet v 1 and then treated with either ST alone, ST[rBet v 1], or the combination of ST and rBet v 1, for 20 days. After 2 aerosol challenges, Treg frequency, in vitro allergen-induced cytokines, rBet v 1-specific IgE and IgG2a, and bronchial histology were made in harvested spleen, sera, and lung. Results were compared with those obtained from not-treated/sensitized mice. ST[rBet v 1] induced immunological and histological changes typical of successful SIT: increased frequency of Tregs and expression of Foxp3; decreased allergen-specific IgE/IgG2a ratio; decrease of in vitro rBet v 1-induced IL-4 from spleen cells; increased allergen-induced IL-10 and IFN-γ; drop of bronchial eosinophilia. ST and ST+rBet v 1 combination, even though induced a slight increase in the frequency of Tregs and moderate allergen-induced IL-10, were ineffective in reducing bronchial eosinophilia, allergen induced IL-4 and rBet v 1-specific IgE/IgG2a ratio. ST[rBet v 1] has tolerogenic and Th-1 skewing properties and efficiently delivers the allergen to the gut immune-system restraining and readdressing the established specific Th2 response toward the allergen in mice.
authors.affiliation: Unit of Immunotoxicology, Allergy and Biosecurity; Center of Ageing Science; Università G. d'Annunzio Foundation; Chieti, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Petrarca
authors.affiliation: Department of Medicine and Ageing Science (DMSI); University G. d'Annunzio of Chieti-Pescara; Chieti, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Clemente
authors.affiliation: Unit of Immuno-oncology; Center of Ageing Science; Università G. d'Annunzio Foundation; Chieti, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Toto
authors.affiliation: Unit of Immuno-oncology; Center of Ageing Science; Università G. d'Annunzio Foundation; Chieti, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.affiliation: Animal Facility; Center of Ageing Science; Università G. d'Annunzio Foundation; Chieti, Italy.
authors.forename: Cosmo
authors.initials: C
authors.lastname: Rossi
authors.affiliation: Research Center; Lofarma SpA; Milano, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zanotta
authors.affiliation: Research Center; Lofarma SpA; Milano, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Mistrello
authors.affiliation: Department of Biotechnology and Biosciences; Università degli Studi di Milano-Bicocca; Milan, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Zanoni
authors.affiliation: Department of Biotechnology and Biosciences; Università degli Studi di Milano-Bicocca; Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Granucci
authors.affiliation: Department of Food, Environmental and Nutritional Sciences (DeFENS); University of Milan; Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Arioli
authors.affiliation: Department of Food, Environmental and Nutritional Sciences (DeFENS); University of Milan; Milan, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Mora
authors.affiliation: Department of Food, Environmental and Nutritional Sciences (DeFENS); University of Milan; Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Guglielmetti
authors.affiliation: Department of Medicine and Ageing Science (DMSI); University G. d'Annunzio of Chieti-Pescara; Chieti, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Paganelli
authors.affiliation: Unit of Immunotoxicology, Allergy and Biosecurity; Center of Ageing Science; Università G. d'Annunzio Foundation; Chieti, Italy; Department of Medicine and Ageing Science (DMSI); University G. d'Annunzio of Chieti-Pescara; Chieti, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Di Gioacchino
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000485:Allergens / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D048249:Streptococcus thermophilus / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D052179:Antigens, Plant; C061312:Bet v 1 allergen, Betula
keywords: Bet v 1; SIT; T regulatory cells; mouse model; streptococcus