Neonatal colonization of germ-free mice with Bifidobacterium longum prevents allergic sensitization to major birch pollen allergen Bet v 1.
The main goal in reversing the allergy epidemic is the development of effective prophylactic strategies. We investigated the prophylactic effect of neonatal mother-to-offspring mono-colonization with Bifidobacterium longum ssp. longum CCM 7952 on subsequent allergic sensitization. Adult male and female germ-free (GF) mice were mono-colonized with B. longum, mated and their offspring, as well as age-matched GF controls, were sensitized with the major birch pollen allergen Bet v 1. Furthermore, signaling pathways involved in the recognition of B. longum were investigated in vitro. Neonatal mono-colonization of GF mice with B. longum suppressed Bet v 1-specific IgE-dependent β-hexosaminidase release as well as levels of total IgE and allergen-specific IgG2a in serum compared to sensitized GF controls. Accordingly, Bet v 1-induced production of both Th1- and Th2-associated cytokines in spleen cell cultures was significantly reduced in these mice. The general suppression of Bet v 1-specific immune responses in B. longum-colonized mice was associated with increased levels of regulatory cytokines IL-10 and TGF-β in serum. In vitro, B. longum induced low maturation status of bone marrow-derived dendritic cells and production of IL-10 in TLR2-, MyD88-, and MAPK-dependent manner. Our data demonstrate that neonatal mono-colonization with B. longum reduces allergic sensitization, likely by activation of regulatory responses via TLR2, MyD88, and MAPK signaling pathways. Thus, B. longum might be a promising candidate for perinatal intervention strategies against the onset of allergic diseases in humans.
Department of Immunology and Gnotobiology, Institute of Microbiology of the Academy of Sciences of the Czech Republic, v. v. i., Novy Hradek, Czech Republic. Electronic address: schwarzer@biomed.cas.cz.
Martin
M
Schwarzer
Dagmar
D
Srutkova
Irma
I
Schabussova
Tomas
T
Hudcovic
Johnnie
J
Akgün
Ursula
U
Wiedermann
Hana
H
Kozakova
D000818:Animals; D052179:Antigens, Plant / Q000276:immunology*; D001644:Bifidobacterium / Q000254:growth & development*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life; D006596:Hexosaminidases / Q000378:metabolism; D006967:Hypersensitivity / Q000517:prevention & control*; D007108:Immune Tolerance; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D052179:Antigens, Plant; D016207:Cytokines; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E; D006596:Hexosaminidases
Allergy; Bifidobacterium; Germ-free mice; Probiotics; TLR2