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

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.