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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.
SUBMITTER: Zhang T
PROVIDER: S-EPMC4481728 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature
The Journal of infectious diseases 20140109 12
<h4>Background</h4>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.<h4>Methods</h4>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-1 ...[more]