Human β‐defensin 3 has immunosuppressive activity in vitro and in vivo

Abstract

β‐defensins are antimicrobial peptides with an essential role in the innate immune response. In addition β‐defensins can also chemoattract cells involved in adaptive immunity. Until now, based on evidence from dendritic cell stimulation, human β defensin‐3 (hBD3) was considered pro‐inflammatory. We present evidence here that hBD3 lacks pro‐inflammatory activity in human and mouse primary Mϕ. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF‐α and IL‐6 accumulation implying an anti‐inflammatory function. hBD3 also inhibits CD40/IFN‐γ stimulation of Mϕ and in vivo, hBD3 significantly reduces the LPS‐induced TNF‐α level in serum. Recent work has revealed that hBD3 binds melanocortin receptors but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation.

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