title: The immune-enhancing effect of the Cronobacter sakazakii ES2 phage results in the activation of nuclear factor-κB and dendritic cell maturation via the activation of IL-12p40 in the mouse bone marrow.
abstract: The bacteriophage ES2 is a virus for bacterial host cells. Unlike other phages that are known for their therapeutic effects, the ES2 phage has never been clearly examined as a therapeutic agent. To systematically and conclusively evaluate its therapeutic efficacy, the expression of the surface markers CD86, CD40, and MHCII, the production of the proinflammatory cytokines IL-6, IL-1α, IL-1β, and TNF-α, and the underlying NF-κB signaling pathway in murine bone marrow-derived dendritic cells (BM-DCs) in response to ES2 phage infection were examined. The bacteriophage ES2, which was isolated from swine fecal samples an antigen, affected the expression of the cell surface molecules and proinflammatory cytokines that are associated with the DC maturation processes. Treatment with ES2 phage also led to NF-κBp65 activation and translocation to the nucleus, which indicates the activation of NF-κB signaling. Furthermore, the ES2 phage induced the promoter activity of IL-12p40. Our chromatin immunoprecipitation assay revealed that p65 was enriched at the IL12-p40 promoter as a direct target of chromatin. The present study demonstrates that the ES2 phage potently induces DC maturation via immune-enhancement processes.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Anam-Dong, Sungbuk-Gu, Seoul 136-701, South Korea.
authors.forename: Tae-Woo
authors.initials: TW
authors.lastname: An
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Anam-Dong, Sungbuk-Gu, Seoul 136-701, South Korea.
authors.forename: Sun-Joong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Food and Biotechnology, College of Engineering, Gachon University, Sungnam 461-701, South Korea.
authors.forename: Young-Duck
authors.initials: YD
authors.lastname: Lee
authors.affiliation: Department of Food and Biotechnology, College of Engineering, Gachon University, Sungnam 461-701, South Korea.
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Anam-Dong, Sungbuk-Gu, Seoul 136-701, South Korea. Electronic address: hichang@korea.ac.kr.
authors.forename: Hyo-Ihl
authors.initials: HI
authors.lastname: Chang
mesh_terms: D000818:Animals; D001435:Bacteriophages / Q000276:immunology* / Q000302:isolation & purification; D002454:Cell Differentiation / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism; D044083:Cronobacter sakazakii / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053762:Interleukin-12 Subunit p40; D016328:NF-kappa B
keywords: Bacteriophage ES2; ChIP; DC; Dendritic cells; ELISA; FITC; IL-12p40; NF-κBp65; PE; chromatin immunoprecipitation; dendritic cell; enzyme-linked immunosorbent assays; fluoresceinisothiocyanate; phycoerythrin