Pasteurization of milk proteins promotes allergic sensitization by enhancing uptake through Peyer's patches

F. Roth-Walter, M. C. Berin, P. Arnaboldi, C. R. Escalante, S. Dahan, J. Rauch, E. Jensen-Jarolim, L. Mayer

Research output: Contribution to journalArticlepeer-review

184 Scopus citations


Background: The underlying mechanisms responsible for allergic sensitization to food proteins remain elusive. To investigate the intrinsic properties (as well as the effect of pasteurization) of the milk proteins α-lactalbumin, β-lactoglobulin and casein that promote the induction of milk allergy. Methods: Alteration of structure and immune-reactivity of native and pasteurized proteins was assessed by gel filtration and ELISA. Uptake of these proteins was compared in vitro and in vivo. The biological effect was assessed by orally sensitizing C3H/HeJ mice with milk proteins followed by a graded oral challenge. Required dose to induce anaphylaxis, symptoms and mean body temperature was recorded. Antigen-specific antibodies and cytokine production by splenocytes were analyzed. Results: Soluble β-lactoglobulin and α-lactalbumin but not insoluble casein were readily transcytosed through enterocytes in vitro and in vivo. Pasteurization caused aggregation of β-lactoglobulin and α-lactalbumin inhibiting uptake by intestinal epithelial cells in vitro and in vivo. Furthermore, aggregation redirected uptake to Peyer's patches, which promoted significantly higher Th2-associated antibody and cytokine production in mice than their native counterparts. Despite this only the soluble forms of β-lactoglobulin and α-lactalbumin elicited anaphylaxis (following priming) when allergens were administered orally. Aggregated β-lactoglobulin and α-lactalbumin as well as casein required systemic administration to induce anaphylaxis. Conclusions: These results indicate that triggering of an anaphylactic response requires two phases (1) sensitization by aggregates through Peyer's patches and (2) efficient transfer of soluble protein across the epithelial barrier. As the majority of common food allergens tend to form aggregates, this may be of clinical importance.

Original languageEnglish
Pages (from-to)882-890
Number of pages9
JournalAllergy: European Journal of Allergy and Clinical Immunology
Issue number7
StatePublished - Jul 2008


  • Anaphylaxis
  • Antigen uptake
  • Milk allergy
  • Oral sensitization
  • Peyer's patches


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