Micro-balancing innate immunity to Salmonella.

EMBO J 30 10, 1977–1989 (2011); published online April 05 2011 MicroRNAs are 19–24 nt-long RNAs that post-transcriptionally regulate eukaryotic gene expression. Beside their important roles in patterning and development, miRNAs also orchestrate responses to pathogen infections. In this issue of , Schulte et al (2011) investigate the miRNA response of mammalian cells to the intracellular bacterium . They find that triggers highly specific and robust alterations to the expression of a subset of host miRNAs. In macrophages, these alterations notably include the rapid downregulation of let-7 gene family members, following extracellular sensing of bacterial lipopolysaccharides (LPS) via Toll-like receptor 4 (TLR4). The authors identify two interleukins (IL-6 and IL-10) as novel targets of Let-7 and suggest that infection rapidly relieves IL-6 and IL-10 from negative control by let-7, thereby potentiating the immune response. Intriguingly, while IL-6 is pro-inflammatory, IL-10 prevents the detrimental consequences of systemic inflammation, suggesting that the observed response is tightly balanced and, hence, biologically relevant.