Oral administration of recombinant Lactococcus lactis expressing bovine β-lactoglobulin partially prevents mice from sensitization

• Published in: Clinical and experimental allergy Vol. 35; no. 4; pp. 539 - 546
• Main Authors: Adel-Patient, K., Ah-Leung, S., Creminon, C., Nouaille, S., Chatel, J.-M., Langella, P., Wal, J.-M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-04-2005; Blackwell; Wiley
• Subjects: Administration, Oral; Allergens - immunology; Allergic diseases; Animals; Antibody Specificity - immunology; Biological and medical sciences; bovine β-lactoglobulin; Cattle; Cytokines - immunology; Feces - chemistry; Female; Food Hypersensitivity - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immune Tolerance - immunology; Immunoglobulin A - immunology; Immunoglobulin E - immunology; Immunoglobulin G - immunology; immunomodulation; Immunopathology; Interferon-gamma - immunology; Lactococcus lactis; Lactococcus lactis - immunology; Lactoglobulins - administration & dosage; Lactoglobulins - biosynthesis; Life Sciences; Medical sciences; Mice; Mice, Inbred BALB C; oral prevention; Recombination, Genetic; Th1 Cells - immunology; Immunopathology; Allergy; Lactococcus lactis; oral prevention; Bovine; Immunomodulation; Rodentia; Oral administration; bovine β-lactoglobulin; Prevention; Streptococcaceae; Vertebrata; Immunology; Mammalia; Lactoglobulins; Mouse; Animal; Bacteria; Micrococcales; Sensitization; Artiodactyla; Recombinant protein; Ungulata; PROBIOTIC; BOVINE BETA-LACTOGLOBULIN; IMMUNOMODULATION; LACTOCOCCUS LACTIS
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2005.02225.x

Summary
Background
The use of probiotics such as Lactococcus lactis and other lactic acid bacteria (LAB) has been proposed for the management of food allergy. However, no experimental study has clearly demonstrated any preventive or therapeutic inhibition of an allergen‐specific IgE response.
Objective
We aimed to study the immunomodulatory effect of recombinant L. lactis expressing bovine β‐lactoglobulin (BLG), a major cow's milk allergen, in a validated mouse model of allergy.
Methods
Six‐week‐old female Balb/c mice received five repeated doses of BLG, of L. lactis plus BLG, or of recombinant L. lactis by gavage. Different recombinant strains were inoculated, which corresponded to BLG doses ranging from 4 to 70 μg/mice. Mice were then sensitized by intra‐peritoneal injection of BLG emulsified in incomplete Freund's adjuvant to induce high IgE concentrations.
Results
Pre‐treatment with natural L. lactis plus BLG allowed induction of BLG‐specific T‐helper type 1 (Th1) response, and abrogated the oral tolerance induced by BLG alone, demonstrating the adjuvant effect of this non‐colonizing LAB. Moreover, pre‐treatment with some of the recombinant strains favoured the development of a Th1 response inhibiting the Th2 one: it induced a significant decrease of specific IgE response, and an intense increase of specific IgG2a and IFN‐γ productions. The most efficient strains that inhibited the IgE response were those producing the highest amounts of the BLG protein.
Conclusion
Oral administration of some recombinant L. lactis was demonstrated to induce a specific Th1 response down‐regulating a further Th2 one. Prophylaxis protocols will thus be evaluated using the most efficient strains.