Premium
Helicobacter pylori and its secreted immunomodulator VacA protect against anaphylaxis in experimental models of food allergy
Author(s) -
Kyburz A.,
Urban S.,
Altobelli A.,
Floess S.,
Huehn J.,
Cover T. L.,
Müller A.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12996
Subject(s) - immunology , helicobacter pylori , immunoglobulin e , food allergy , allergy , sensitization , foxp3 , biology , medicine , immune system , antibody , genetics
Summary Background Food allergy is an increasingly common health problem in Western populations. Epidemiological studies have suggested both positive and negative associations between food allergy and infection with the gastric bacterium Helicobacter pylori . Objective The objective of this work was to investigate whether experimental infection with H. pylori , or prophylactic treatment with H. pylori ‐derived immunomodulatory molecules, affects the onset and severity of food allergy, either positively or negatively. Methods We infected neonatal C57 BL /6 or C3H mice with H. pylori or treated animals with H. pylori components (bacterial lysate or the immunomodulator VacA) and subsequently subjected them to four different protocols for food allergy induction, using either ovalbumin or peanut extract as allergens for sensitization and challenge. Readouts included anaphylaxis scoring, quantification of allergen‐specific serum IgE and IgG1 and of the mast cell protease MCPT 1, as well as splenic T‐helper‐2 cell‐derived cytokine production. Mesenteric lymph node CD 4 + FoxP3 + regulatory T cells were subjected to flow cytometric quantification and sorting followed by qRT ‐ PCR , and to DNA methylation analyses of the Treg‐specific demethylated region ( TSDR ) within the FOXP 3 locus. Results Mice that had been infected with H. pylori or treated with H. pylori ‐derived immunomodulators showed reduced anaphylaxis upon allergen sensitization and challenge, irrespective of the allergen used. Most of the immunologic assays confirmed a protective effect of H. pylori . CD 4 + FoxP3 + T cells were more abundant in protected mice and exhibited a stable Treg phenotype characterized by FOXP 3 TSDR demethylation. Conclusions and Clinical Relevance Helicobacter pylori confers protection against the anaphylaxis associated with ovalbumin and peanut allergy and affects the epigenome of T cells, thereby promoting stable Treg differentiation and functionality. Prophylactic treatment with H. pylori ‐derived immunomodulators appears to be a promising strategy for food allergy prevention.