title: Salmonella enterica serovar enteritidis modulates intestinal epithelial miR-128 levels to decrease macrophage recruitment via macrophage colony-stimulating factor.
abstract: BACKGROUND
  The mechanism underlying the ability of virulent Salmonella organisms to escape clearance by macrophages is incompletely understood. Here, we report a novel mechanism by which Salmonella escapes macrophages.
  
  
  METHODS
  Microarray and quantitative real-time polymerase chain reaction analyses were used to screen key microRNAs regulating Salmonella-host cell interactions. Target gene was tested using luciferase reporter and Western blot assays. The role of microRNA 128 (miR-128) was assayed using intestinal epithelial cells and a mouse infection model.
  
  
  RESULTS
  The miR-128 level in human intestinal epithelial HT29 cells was strongly increased by infection with strain SE2472, and the elevation in miR-128 levels in mouse intestine and colon tissues correlated with the level of Salmonella infection in mice. Macrophage colony-stimulating factor (M-CSF) was identified as a target of miR-128, and increased miR-128 levels in epithelial cells due to infection with strain SE2472 significantly decreased the level of cell-secreted M-CSF, leading to impaired M-CSF-mediated macrophage recruitment. The secreted proteins from Salmonella were identified as possible effectors to induce miR-128 expression via the p53 signaling pathway. Moreover, intragastric delivery of anti-miR-128 antagomir into mice significantly increased M-CSF-mediated macrophage recruitment and suppressed Salmonella infection.
  
  
  CONCLUSIONS
  Salmonella can upregulate intestinal epithelial miR-128 expression, which, in turn, decreases levels of epithelial cell-secreted M-CSF and M-CSF-induced macrophage recruitment.
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
authors.forename: Tianfu
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Yu
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Virology, University of California School of Public Health, Berkeley.
authors.forename: Fenyong
authors.initials: F
authors.lastname: Liu
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gu
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012480:Salmonella Infections / Q000517:prevention & control; D012477:Salmonella enteritidis / Q000254:growth & development / Q000302:isolation & purification*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C550324:Mirn128 microRNA, mouse; D016159:Tumor Suppressor Protein p53; D016173:Macrophage Colony-Stimulating Factor
keywords: M-CSF; Salmonella; infection; macrophage; miR-128