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Gewählte Publikation:

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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2014

AutorInnen: Roth-Walter, F; Pacios, LF; Gomez-Casado, C; Hofstetter, G; Roth, GA; Singer, J; Diaz-Perales, A; Jensen-Jarolim, E

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

Quelle: PLoS One. 2014; 9(8):e104803



Autor/innen der Vetmeduni Vienna:

Hofstetter Gerlinde
Jensen-Jarolim Erika
Roth-Walter Franziska

Beteiligte Vetmed-Organisationseinheiten
Messerli Forschungsinstitut, Abteilung für Komparative Medizin


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.

Keywords Pubmed: Allergens/immunology*
Allergens/metabolism
Animals
Apoptosis/immunology
Flavonoids/metabolism
Humans
Iron/metabolism*
Leukocytes, Mononuclear/immunology
Lipocalins/immunology*
Lipocalins/metabolism
Lymphocyte Activation/immunology
Milk/immunology
Milk Hypersensitivity/immunology*
Siderophores/immunology
Siderophores/metabolism*
T-Lymphocytes, Helper-Inducer/immunology*


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