Zwirner J. beta-defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved

Abstract

Abstractβ‐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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