Bifidobacterium bifidum NCC 453 promotes tolerance induction in murine models of sublingual immunotherapy

Int Arch Allergy Immunol. 2012;158(1):35-42. doi: 10.1159/000330101. Epub 2011 Dec 28.

Abstract

Background: Enhancing clinical efficacy remains a major goal in allergen-specific immunotherapy. In this study, we tested three strains of bifidobacteria as candidate adjuvants for sublingual allergy vaccines.

Methods: Probiotic candidates were evaluated in human monocyte-derived dendritic cell (h-DC) maturation and CD4(+) T-cell polarization in vitro models and further tested in murine models of sublingual immunotherapy in BALB/c mice sensitized to either ovalbumin or birch pollen.

Results: Bifidobacterium adolescentis, B. bifidum and B. longum induced h-DC maturation and polarized naïve CD4(+) T cells toward interferon-γ and interleukin-10 production. B. bifidum increased CD25(high), Foxp3(+) cells within CD4(+) T lymphocytes and was the most potent inducer of interferon-γ in Th2-skewed peripheral blood mononuclear cells and h-DC T-cell cocultures. It also induced a significant decrease in airway hyperresponsiveness in BALB/c mice sensitized to ovalbumin. Sublingual administration of B. bifidum together with recombinant Bet v 1 enhanced tolerance induction in BALB/c mice sensitized to birch pollen, with a downregulation of both airway hyperresponsiveness, lung inflammation and Bet v 1-specific Th2 responses.

Conclusions: Due to its capacity to reorient established Th2 responses toward Th1/regulatory T-cell profiles, B. bifidum represents a valid candidate adjuvant for specific immunotherapy of type I allergies.

MeSH terms

  • Administration, Sublingual
  • Allergens / immunology
  • Animals
  • Antigens, Plant / immunology
  • Bifidobacterium / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / microbiology
  • Desensitization, Immunologic*
  • Down-Regulation
  • Female
  • Humans
  • Immune Tolerance*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Pollen / immunology
  • Probiotics*

Substances

  • Allergens
  • Antigens, Plant
  • IL10 protein, mouse
  • Bet v 1 allergen, Betula
  • Interleukin-10
  • Interferon-gamma
  • Ovalbumin