Premium
Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let‐7 family
Author(s) -
Schulte Leon N,
Eulalio Ana,
Mollenkopf HansJoachim,
Reinhardt Richard,
Vogel Jörg
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.94
Subject(s) - biology , salmonella , microrna , host (biology) , host response , genetics , gene , immune system , bacteria
MicroRNAs have well‐established roles in eukaryotic host responses to viruses and extracellular bacterial pathogens. In contrast, microRNA responses to invasive bacteria have remained unknown. Here, we report cell type‐dependent microRNA regulations upon infection of mammalian cells with the enteroinvasive pathogen, Salmonella Typhimurium. Murine macrophages strongly upregulate NF‐κB associated microRNAs; strikingly, these regulations which are induced by bacterial lipopolysaccharide (LPS) occur and persist regardless of successful host invasion and/or replication, or whether an inflammatory response is mounted, suggesting that microRNAs belong to the first line of anti‐bacterial defence. However, a suppression of the global immune regulator miR‐155 in endotoxin‐tolerant macrophages revealed that microRNA responses also depend on the status of infected cells. This study identifies the let‐7 family as the common denominator of Salmonella ‐regulated microRNAs in macrophages and epithelial cells, and suggests that repression of let‐7 relieves cytokine IL‐6 and IL‐10 mRNAs from negative post‐transcriptional control. Our results establish a paradigm of microRNA‐mediated feed‐forward activation of inflammatory factors when mammalian cells are targeted by bacterial pathogens.