title: The synthetic peptides bovine enteric β-defensin (EBD), bovine neutrophil β-defensin (BNBD) 9 and BNBD 3 are chemotactic for immature bovine dendritic cells.
abstract: Human and murine immature DCs (iDCs) are highly efficient in antigen capture and processing, while as mature cells they present antigen and are potent initiators of cell-mediated immune responses. Consequently, iDCs are logical targets for vaccine antigens. Originally discovered for their antimicrobial activity, and thought of as strictly part of the innate immune system, studies with defensins such as human β (beta)-defensin 2 (hBD2) and murine β-defensin 2 (mBD2) have shown that they can function as chemo-attractant for iDCs and, in vaccination strategies, can enhance antigen-specific adaptive immune responses. Most studies to date have been conducted in mice. In contrast, little is known about defensins in cattle. To expand our understanding of the role of defensins in modulating immune responses in cattle, DCs were generated from bovine monocytes and the immature state of these bovine DCs was characterized phenotypically and through functional assays. By day 3 (DC3), bovine monocyte-derived DCs stained positively for DC-specific receptors CD1, CD80/86, CD205, DC-Lamp and MMR. When compared to conventional 6-day DC cultures or DCs cultured for 10 days with and without maturation factors, these DC3 were functionally at their most immature stage. Fourteen of the 16 known bovine β-defensins were synthesized and the synthetic peptides were screened for their ability to attract bovine iDCs. Bovine DC3 were consistently attracted to BNBD3, an analog of BNBD3 (aBNBD3), BNBD9 and bovine EBD in vitro and to aBNBD3 in vivo. These results are the first to describe chemotactic ability of synthetic bovine β-defensins for immature bovine monocyte-derived DCs.
authors.affiliation: Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mackenzie-Dyck
authors.forename: Sam
authors.initials: S
authors.lastname: Attah-Poku
authors.forename: Veronique
authors.initials: V
authors.lastname: Juillard
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Babiuk
authors.forename: Sylvia
authors.initials: S
authors.lastname: van Drunen Littel-van den Hurk
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002417:Cattle / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D002633:Chemotaxis / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D016130:Immunophenotyping; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000276:immunology; D023083:beta-Defensins / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D004220:Disulfides; D023083:beta-Defensins