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.
Stallergènes SA, Antony, France.
Hélène
H
Moussu
Laurence
L
Van Overtvelt
Stéphane
S
Horiot
Sophie
S
Tourdot
Sabi
S
Airouche
Adrian
A
Zuercher
Sébastien
S
Holvoet
Guénolée
G
Prioult
Sophie
S
Nutten
Annick
A
Mercenier
Laurent
L
Mascarell
Philippe
P
Moingeon
D000286:Administration, Sublingual; D000485:Allergens / Q000276:immunology; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology; D001644:Bifidobacterium / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D003888:Desensitization, Immunologic; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011058:Pollen / Q000276:immunology; D019936:Probiotics
D000485:Allergens; D052179:Antigens, Plant; C556062:IL10 protein, mouse; C061312:Bet v 1 allergen, Betula; D016753:Interleukin-10; D007371:Interferon-gamma; D010047:Ovalbumin