The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron

Franziska Roth-Walter, Luis F. Pacios, Cristina Gomez-Casado, Gerlinde Hofstetter, Georg A. Roth, Josef Singer, Araceli Diaz-Perales, Erika Jensen-Jarolim

Research output: Journal article (peer-reviewed)Journal article

54 Citations (Scopus)

Abstract

The mechanisms of allergic sensitization to milk are still elusive. The major allergen Bos d 5 belongs to the lipocalin-family and thus is able to transport numerous ligands. In this study we investigated its ability to bind to iron-siderophore complexes and tested the immune-modulatory properties of Bos d 5 in either forms. Structural and in silico docking analysis of Bos d 5 revealed that Bos d 5 is able to bind to iron via catechol-based flavonoids (quercetin, myricetin, luteolin) that act as siderophores as confirmed by spectral-analysis and iron staining. Calculated dissociation constants of docking analyses were below 1 μM by virtual addition of iron. When incubated with human peripheral blood mononuclear cells (PBMCs), only the apo-form of Bos d 5 led to an increase of CD4+positive cells and significantly elevated IL13 and IFNγ-levels. In contrast, holo-Bos d 5 decreased numbers of CD4 expressing cells and induced apoptosis. Taken together, our data give evidence that Bos d 5 is capable of binding iron via siderophores. Moreover, our data support for the first time the notion that the form of application (apo- or holo-form) is decisive for the subsequent immune response. The apo-form promotes Th2 cells and inflammation, whereas the holo-form appears to be immunosuppressive.

Original languageEnglish
Article numbere104803
JournalPLoS ONE
Volume9
Issue number8
DOIs
Publication statusPublished - 12 Aug 2014
Externally publishedYes

ASJC Scopus subject areas

  • Multidisciplinary

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