title: HBD-3 induces NK cell activation, IFN-γ secretion and mDC dependent cytolytic function.
abstract: We previously showed that human beta defensin-3 (hBD-3) activates mDC via TLR1/2. Here we investigated the effects of hBD-3 on NK cell activation state and effector functions. We observed that hBD-3 activates PBMC to secrete IFN-γ and kill K562 and HUH hepatoma target cells in an NK dependent fashion, and both TLR1/2 and CCR2 are involved. TLR1, TLR2 and CCR2 were expressed on NK cells, and in purified NK culture experiments we observed hBD-3 to directly act on NK cells, resulting in CD69 upregulation and IFNγ secretion. We also observed mDC-hBD-3 enhanced NK cytolytic activity and IFNγ production. These results implicate hBD-3 in its ability to directly activate NK cells and increase NK cell effector function, as well as promote mDC-dependent NK activity. HBD-3 may therefore act as a mediator of innate cell interactions that result in bridging of innate and adaptive immunity.
authors: Department of Medicine, Case Western Reserve University, Cleve, OH, United States; Department of Pathology, Case Western Reserve University, Cleve, OH, United States.
authors: Chelsey J
authors: CJ
authors: Judge
authors: Department of Pathology, Case Western Reserve University, Cleve, OH, United States.
authors: Elane
authors: E
authors: Reyes-Aviles
authors: Department of Medicine, Case Western Reserve University, Cleve, OH, United States.
authors: Sara J
authors: SJ
authors: Conry
authors: Department of Medicine, Case Western Reserve University, Cleve, OH, United States.
authors: Scott S
authors: SS
authors: Sieg
authors: Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleve, OH, United States.
authors: Zhimin
authors: Z
authors: Feng
authors: Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleve, OH, United States.
authors: Aaron
authors: A
authors: Weinberg
authors: Department of Medicine, Case Western Reserve University, Cleve, OH, United States; Department of Pathology, Case Western Reserve University, Cleve, OH, United States; Divisions of Infectious and Rheumatic Diseases, University Hospitals Case Medical Center, The Cleveland VA Medical Center, and the Center for AIDS Research, United States. Electronic address: dda3@case.edu.
authors: Donald D
authors: DD
authors: Anthony
mesh_terms: D056704:Adaptive Immunity; D002450:Cell Communication / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D054390:Receptors, CCR2 / Q000276:immunology; D051194:Toll-Like Receptor 1 / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D023083:beta-Defensins / Q000276:immunology*
chemical_list: C515334:CCR2 protein, human; C422950:DEFB103A protein, human; D054390:Receptors, CCR2; C495342:TLR2 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D023083:beta-Defensins; D007371:Interferon-gamma
keywords: Defensin; Dendritic cell; Human; Immunity; Innate; Natural killer cell