Human β‐defensin 3 increases the TLR9‐dependent response to bacterial DNA. Issue 4 (14th February 2017)

• Record Type: Journal Article
• Authors: McGlasson, Sarah L.; Semple, Fiona; MacPherson, Heather; Gray, Mohini; Davidson, Donald J.; Dorin, Julia R.
• Is Part Of: European journal of immunology. Volume 47:Issue 4(2017)
• Page Start: 658
• Page End: 664
• Publication Date: 2017-02-14
• Subjects: Antimicrobial peptide -- β‐Defensin -- Dendritic cells -- Plasmacytoid dendritic cells -- Toll like receptor 9 -- Type I interferon; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201646799
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : Bacterial DNA stimulates a TLR9‐dependent immune response in human and mouse immune cells. hBD3 increases the uptake of bacterial DNA into dendritic cells and amplifies the immune response. The effect of hBD3 on the cellular response to DNA could be harnessed to increase the efficiency of DNA‐vaccines and immunotherapies. Abstract : Human β‐defensin 3 (hBD3) is a cationic antimicrobial peptide with potent bactericidal activity in vitro. HBD3 is produced in response to pathogen challenge and can modulate immune responses. The amplified recognition of self‐DNA by human plasmacytoid dendritic cells has been previously reported, but we show here that hBD3 preferentially enhances the response to bacterial DNA in mouse Flt‐3 induced dendritic cells (FLDCs) and in human peripheral blood mononuclear cells. We show the effect is mediated through TLR9 and although hBD3 significantly increases the cellular uptake of both E. coli and self‐DNA in mouse FLDCs, only the response to bacterial DNA is enhanced. Liposome transfection also increases uptake of bacterial DNA and amplifies the TLR9‐dependent response. In contrast to hBD3, lipofection of self‐DNA enhances inflammatory signaling, but the response is predominantly TLR9‐independent. Together, these data show that hBD3 has a role in the innate immune‐mediated response to pathogen DNA, increasing inflammatory signaling and promoting activation of the adaptive immune system via antigen presenting cells including dendritic cells. Therefore, our data identify an additional immunomodulatory role for this copy‐number variable defensin, of relevance to host defence against infection and indicate a potential for the inclusion of HBD3 in pathogen DNA‐based vaccines.