β-Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved

Authors

  • Afsaneh Soruri,

    1. Department of Cellular and Molecular Immunology, Georg-August-University Göttingen, Göttingen, Germany
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    • These two authors contributed equally to this work.

  • Jasmin Grigat,

    1. Department of Cellular and Molecular Immunology, Georg-August-University Göttingen, Göttingen, Germany
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    • These two authors contributed equally to this work.

  • Ulf Forssmann,

    1. IPF PharmaCeuticals, Hannover Medical School, Hannover, Germany
    2. Center of Pharmacology and Toxicology, Hannover Medical School, Hannover, Germany
    3. Merck KGaA, Darmstadt, Germany
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    • These two authors contributed equally to this work.

  • Joachim Riggert,

    1. Department of Transfusion Medicine, Georg-August-University Göttingen, Göttingen, Germany
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  • Jörg Zwirner Dr.

    Corresponding author
    1. Department of Cellular and Molecular Immunology, Georg-August-University Göttingen, Göttingen, Germany
    • Department of Cellular and Molecular Immunology, Georg-August-University Göttingen, Humboldtallee 34, D-37073 Göttingen, Germany, Fax: +49-551-395-843
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Abstract

β-Defensins are natural peptide antibiotics whose immunomodulatory functions are poorly understood. In the present study, macrophages were found to migrate to human β-defensins (HBD)-1 to -4 using Gαi proteins as well as MAPK ERK, p38 and JNK as signal transducers. In addition, mast cells responded to HBD-1 to -4 with calcium fluxes as well as chemotaxis, which increased upon stimulation with IgE plus antigen or ionomycin. In contrast, human β-defensins were unable to induce migration of memory lymphocytes and dendritic cells (DC). Similar to HBD, the murine β-defensin (mBD)-8 mobilized macrophages and lacked the ability to recruit memory T cells. These findings were unexpected as CCR6 on memory T cells and DC has been previously observed to be a receptor for human β-defensins. In support of our findings, however, RBL-2H3 as well as 300.19 cells stably expressing CCR6 proved to be unresponsive to HBD-2 and -3. Intriguingly, our observation of a PKC-independent homologous desensitization between HBD-1 to -4 suggests a common receptor for HBD. In summary, chemoattraction of macrophages and mast cells is evolutionary conserved within the β-defensin family despite a considerable sequence variation and distinct antimicrobial activities. However, CCR6 is not a functional receptor for β-defensins.

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