The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron.
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 o...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0104803&type=printable |
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| author | Franziska Roth-Walter Luis F Pacios Cristina Gomez-Casado Gerlinde Hofstetter Georg A Roth Josef Singer Araceli Diaz-Perales Erika Jensen-Jarolim |
| author_facet | Franziska Roth-Walter Luis F Pacios Cristina Gomez-Casado Gerlinde Hofstetter Georg A Roth Josef Singer Araceli Diaz-Perales Erika Jensen-Jarolim |
| author_sort | Franziska Roth-Walter |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2edba4badea94f30874a202c2adc438d |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-2edba4badea94f30874a202c2adc438d2025-08-20T03:46:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10480310.1371/journal.pone.0104803The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron.Franziska Roth-WalterLuis F PaciosCristina Gomez-CasadoGerlinde HofstetterGeorg A RothJosef SingerAraceli Diaz-PeralesErika Jensen-JarolimThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0104803&type=printable |
| spellingShingle | Franziska Roth-Walter Luis F Pacios Cristina Gomez-Casado Gerlinde Hofstetter Georg A Roth Josef Singer Araceli Diaz-Perales Erika Jensen-Jarolim The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron. PLoS ONE |
| title | The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron. |
| title_full | The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron. |
| title_fullStr | The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron. |
| title_full_unstemmed | The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron. |
| title_short | The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron. |
| title_sort | major cow milk allergen bos d 5 manipulates t helper cells depending on its load with siderophore bound iron |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0104803&type=printable |
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