HBD-3 facilitates mDC-NK crosstalk (INC6P.348)

Abstract

Abstract mDC and NK cells are involved in the innate immune response to pathogen, and bidirectional mDC-NK interactions are well described. hBD-3, an anti-microbial peptide, is known to activate mDC via TLR1/2. Here we investigated the effects of hBD-3 on mDC-NK interactions. We observed hBD-3 to activate PBMC to secrete IFN-γ and kill K562 and HUH hepatoma target cells in an mDC and NK dependent fashion, and both TLR1/2 and CCR2 were involved. In purified mDC-NK coculture experiments we observed hBD-3 to facilitate mDC and NK activation, IFNγ secretion, and killer activity. Activity was variable among healthy subject samples, in some cases dependent on TLR1/2, and in other cases dependent on CCR2. We observed TLR1/2 and CCR2 expression on both mDC and NK cells, with variability in expression among individuals. These results implicate hBD-3 in ability to directly activate NK cells, mDC, and facilitate mDC-NK interactions. HBD3 may therefore act as a mediator of innate cell interactions that result in bridging of innate and adaptive immunity.