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J Infect Dis. 2014 Jun 15;209(12):2000-11. doi: 10.1093/infdis/jiu006. Epub 2014 Jan 9.

Salmonella enterica serovar enteritidis modulates intestinal epithelial miR-128 levels to decrease macrophage recruitment via macrophage colony-stimulating factor.

Author information

  • 1Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
  • 2Department of Virology, University of California School of Public Health, Berkeley.

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.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

KEYWORDS:

M-CSF; Salmonella; infection; macrophage; miR-128

PMID:
24415783
[PubMed - indexed for MEDLINE]
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