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 beta-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 IgG(1) 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.
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 murineIL-10 could prevent sensitization in a mouse model of food allergy. METHODS: Before each oral sensitization with beta-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 IgG(1) 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.
Authors: Richard T Strait; Ashley Mahler; Simon Hogan; Marat Khodoun; Akira Shibuya; Fred D Finkelman Journal: J Allergy Clin Immunol Date: 2011-02-26 Impact factor: 10.793
Authors: Florence Brüll; Ronald P Mensink; Karin van den Hurk; Adriaan Duijvestijn; Jogchum Plat Journal: J Biol Chem Date: 2009-11-30 Impact factor: 5.157