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Hum Vaccin Immunother. 2014;10(5):1228-37. doi: 10.4161/hv.28155. Epub 2014 Mar 6.

rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant.

Author information

1
Unit of Immunotoxicology, Allergy and Biosecurity; Center of Ageing Science; Università G. d'Annunzio Foundation; Chieti, Italy.
2
Department of Medicine and Ageing Science (DMSI); University G. d'Annunzio of Chieti-Pescara; Chieti, Italy.
3
Unit of Immuno-oncology; Center of Ageing Science; Università G. d'Annunzio Foundation; Chieti, Italy.
4
Animal Facility; Center of Ageing Science; Università G. d'Annunzio Foundation; Chieti, Italy.
5
Research Center; Lofarma SpA; Milano, Italy.
6
Department of Biotechnology and Biosciences; Università degli Studi di Milano-Bicocca; Milan, Italy.
7
Department of Food, Environmental and Nutritional Sciences (DeFENS); University of Milan; Milan, Italy.
8
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.

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.

KEYWORDS:

Bet v 1; SIT; T regulatory cells; mouse model; streptococcus

PMID:
24603094
PMCID:
PMC4896610
DOI:
10.4161/hv.28155
[Indexed for MEDLINE]
Free PMC Article

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