The Journal of Allergy and Clinical Immunology
Volume 119, Issue 4 , Pages 952-959, April 2007

Oral administration of an IL-10–secreting Lactococcus lactis strain prevents food-induced IgE sensitization

  • Christophe P. Frossard, PhD

      Affiliations

    • From the University Hospital of Geneva, Department of Pediatrics
  • ,
  • Lothar Steidler, PhD

      Affiliations

    • Alimentary Pharmabiotic Center, University College Cork
  • ,
  • Philippe A. Eigenmann, MD

      Affiliations

    • From the University Hospital of Geneva, Department of Pediatrics
    • Corresponding Author InformationReprint requests: Philippe A. Eigenmann, MD, University Hospital of Geneva, Department of Pediatrics, 6 rue Willy-Donze, 1211 Geneva 14, Switzerland.

Received 6 February 2006; received in revised form 4 December 2006; accepted 11 December 2006. published online 06 March 2007.

Geneva, Switzerland, and Cork, Ireland

Background

Because tolerance to food is potentially modulated by IL-10, strategies to prevent food allergy should favor an increased delivery of IL-10 to the gut.

Objectives

We hypothesized that administration of a Lactococcus lactis transfected to secrete murine IL-10 could prevent sensitization in a mouse model of food allergy.

Methods

Before each oral sensitization with β-lactoglobulin in the presence of cholera toxin, young mice were administered the transfected Lactococcus lactis. Antigen-induced anaphylaxis after oral challenge assessed clinical protection achieved by the pretreatment. Serum and feces antigen-specific antibody concentrations were sequentially measured. Antibody titers were correlated with antibody and IL-10–secreting cell numbers in the spleen and in Peyer patches.

Results

Pretreatment with transfected Lactococcus lactis contributed to diminish anaphylaxis significantly, and inhibit antigen-specific serum IgE and IgG1 production strongly. In addition, transfected Lactococcus lactis increased the production of antigen-specific IgA in the gut. Variations of antibody levels in the serum and the gut correlated with the numbers of antibody-producing cells. In addition, the presence of exogenous IL-10 in the gut by transfected Lactococcus lactis induced IL-10 secretion by Peyer patches cells. Increased IL-10 titers were also measured in the plasma.

Conclusion

These results suggest that a microorganism bioengineered to deliver IL-10 in the gut can decrease food-induced anaphylaxis and provide an option to prevent IgE-type sensitization to common food allergens.

Clinical implications

Nonpathogenic IL-10–producing microorganisms in the gut could have a potential to prevent systemic food-induced anaphylaxis.

Key words: Food hypersensitivity, anaphylaxis, tolerance, T-lymphocytes, β-lactoglobulin, IL-10

Abbreviations used: AU, Arbitrary units, BLG, β-Lactoglobulin, CFU, Cell-forming units, CTX, Cholera toxin, LL-mIL10, Lactococcus lactis transfected with the gene for recombinant murine IL-10, LLwt, Lactococcus lactis wild type

 

 Supported by grants 3200-107752 and 3200-065203 from the Swiss National Science Foundation, and the Helmut Horten Foundation. L. Steidler is supported by the Science Foundation Ireland (SFI/01/F.1/B036).Disclosure of potential conflict of interest: P. A. Eigenmann has consulting arrangements with Phadia and is on the speakers' bureau for Phadia, Trimedal, Milupa, UCB Pharma, Mead Johnson, Fujisawa, Novartis, Abbot, Essex, and Pfizer. L. Steidler has consulting arrangements with VIB, owns stock in Actogenix, has patent licensing arrangements with Actogenix, and is employed by Actogenix. C. P. Frossard has declared that he has no conflict of interest.

PII: S0091-6749(06)03807-3

doi:10.1016/j.jaci.2006.12.615

The Journal of Allergy and Clinical Immunology
Volume 119, Issue 4 , Pages 952-959, April 2007