MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development.

Mammalian noncoding microRNAs (miRNAs) are a class of gene regulators that have been linked to immune system function. Here, we have investigated the role of miR-155 during an autoimmune inflammatory disease. Consistent with a positive role for miR-155 in mediating inflammatory responses, Mir155(-/-) mice were highly resistant to experimental autoimmune encephalomyelitis (EAE). miR-155 functions in the hematopoietic compartment to promote the development of inflammatory T cells including the T helper 17 (Th17) cell and Th1 cell subsets. Furthermore, the major contribution of miR-155 to EAE was CD4(+) T cell intrinsic, whereas miR-155 was also required for optimum dendritic cell production of cytokines that promoted Th17 cell formation. Our study shows that one aspect of miR-155 function is the promotion of T cell-dependent tissue inflammation, suggesting that miR-155 might be a promising therapeutic target for the treatment of autoimmune disorders.

Sociality in Escherichia coli: Enterochelin Is a Private Good at Low Cell Density and Can Be Shared at High Cell Density.

UNLABELLED: Many bacteria produce secreted iron chelators called siderophores, which can be shared among cells with specific siderophore uptake systems regardless of whether the cell produces siderophores. Sharing secreted products allows freeloading, where individuals use resources without bearing the cost of production. Here we show that the Escherichia coli siderophore enterochelin is not evenly shared between producers and nonproducers. Wild-type Escherichia coli grows well in low-iron minimal medium, and an isogenic enterochelin synthesis mutant (ΔentF) grows very poorly. The enterochelin mutant grows well in low-iron medium supplemented with enterochelin. At high cell densities the ΔentF mutant can compete equally with the wild type in low-iron medium. At low cell densities the ΔentF mutant cannot compete. Furthermore, the growth rate of the wild type is unaffected by cell density. The wild type grows well in low-iron medium even at very low starting densities. Our experiments support a model where at least some enterochelin remains associated with the cells that produce it, and the cell-associated enterochelin enables iron acquisition even at very low cell density. Enterochelin that is not retained by producing cells at low density is lost to dilution. At high cell densities, cell-free enterochelin can accumulate and be shared by all cells in the group. Partial privatization is a solution to the problem of iron acquisition in low-iron, low-cell-density habitats. Cell-free enterochelin allows for iron scavenging at a distance at higher population densities. Our findings shed light on the conditions under which freeloaders might benefit from enterochelin uptake systems. IMPORTANCE: Sociality in microbes has become a topic of great interest. One facet of sociality is the sharing of secreted products, such as the iron-scavenging siderophores. We present evidence that the Escherichia coli siderophore enterochelin is relatively inexpensive to produce and is partially privatized such that it can be efficiently shared only at high producer cell densities. At low cell densities, cell-free enterochelin is scarce and only enterochelin producers are able to grow in low-iron medium. Because freely shared products can be exploited by freeloaders, this partial privatization may help explain how enterochelin production is stabilized in E. coli and may provide insight into when enterochelin is available for freeloaders.

Positive Autoregulation of an Acyl-Homoserine Lactone Quorum-Sensing Circuit Synchronizes the Population Response.

Many proteobacteria utilize acyl-homoserine lactone quorum-sensing signals. At low population densities, cells produce a basal level of signal, and when sufficient signal has accumulated in the surrounding environment, it binds to its receptor, and quorum-sensing-dependent genes can be activated. A common characteristic of acyl-homoserine lactone quorum sensing is that signal production is positively autoregulated. We have examined the role of positive signal autoregulation in Pseudomonas aeruginosa We compared population responses and individual cell responses in populations of wild-type P. aeruginosa to responses in a strain with the signal synthase gene controlled by an arabinose-inducible promoter so that signal was produced at a constant rate per cell regardless of cell population density. At a population level, responses of the wild type and the engineered strain were indistinguishable, but the responses of individual cells in a population of the wild type showed greater synchrony than the responses of the engineered strain. Although sufficient signal is required to activate expression of quorum-sensing-regulated genes, it is not sufficient for activation of certain genes, the late genes, and their expression is delayed until other conditions are met. We found that late gene responses were reduced in the engineered strain. We conclude that positive signal autoregulation is not a required element in acyl-homoserine lactone quorum sensing, but it functions to enhance synchrony of the responses of individuals in a population. Synchrony might be advantageous in some situations, whereas a less coordinated quorum-sensing response might allow bet hedging and be advantageous in other situations.IMPORTANCE There are many quorum-sensing systems that involve a transcriptional activator, which responds to an acyl-homoserine lactone signal. In all of the examples studied, the gene coding for signal production is positively autoregulated by the signal, and it has even been described as essential for a quorum-sensing response. We have used the opportunistic pathogen Pseudomonas aeruginosa as a model to show that positive autoregulation is not required for a robust quorum-sensing response. We also show that positive autoregulation of signal production enhances the synchrony of the response. This information enhances our general understanding of the biological significance of how acyl-homoserine lactone quorum-sensing circuits are arranged.