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

Claudia Petrarca, Emanuela Clemente, Valentina Toto, Manuela Iezzi, Cosmo Rossi, Stefania Zanotta, Gianni Mistrello, Ivan Zanoni, Francesca Granucci, Stefania Arioli, Diego Mora, Simone Guglielmetti, Roberto Paganelli, Mario Di Gioacchino

Research output: Contribution to journalArticle

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 allergeninduced 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.

Original languageEnglish
Pages (from-to)1228-1237
Number of pages10
JournalHuman Vaccines and Immunotherapeutics
Volume10
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • Bet v 1
  • Mouse model
  • SIT
  • Streptococcus
  • T regulatory cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Medicine(all)

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  • Cite this

    Petrarca, C., Clemente, E., Toto, V., Iezzi, M., Rossi, C., Zanotta, S., Mistrello, G., Zanoni, I., Granucci, F., Arioli, S., Mora, D., Guglielmetti, S., Paganelli, R., & Di Gioacchino, M. (2014). rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant. Human Vaccines and Immunotherapeutics, 10(5), 1228-1237. https://doi.org/10.4161/hv.28155