Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma.
BACKGROUND
Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far.


OBJECTIVE
The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma.


METHODS
Newborn Balb/c mice received orally 10(9) CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with ovalbumin.


RESULTS
The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes.


CONCLUSIONS
Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-beta production.
Feleszko
W
W
Department of Pediatric Pneumology and Allergy, The Medical University Children's Hospital, Warszawa, Poland. wfeleszko@kliniczny.pl
Jaworska
J
J
Rha
R-D
RD
Steinhausen
S
S
Avagyan
A
A
Jaudszus
A
A
Ahrens
B
B
Groneberg
D A
DA
Wahn
U
U
Hamelmann
E
E
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D001644:Bifidobacterium / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000517:prevention & control; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D019936:Probiotics / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007074:Immunoglobulin G; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E; D010047:Ovalbumin