Dendritic cells (DCs) are important for the initiation and regulation of immune responses. In this study, we demonstrate that DC homeostatic development in peripheral lymphoid organs is negatively regulated by the transcriptional repressor, Blimp-1, which is critical for regulation of plasma cell differentiation and T cell homeostasis and function. Deletion of Prdm1, the gene encoding Blimp-1, in mouse hematopoietic lineages resulted in an increase in the steady-state number of conventional DCs (cDCs). Specifically, Prdm1 deletion increased immediate CD8− cDC precursors in peripheral lymphoid organs, causing selective expansion of the CD8− cDC population. Upon stimulus-induced maturation, Blimp-1 was up-regulated in bone marrow-derived DCs via the p38 MAPK and NF-κB pathways. Notably, Blimp-1-deficient DCs matured poorly upon stimulation in vitro and in vivo. Blimp-1 binds to the proinflammatory cytokine/chemokine genes, Il-6 and Ccl2, and negatively regulates their expression. Collectively, our findings reveal two new roles for Blimp-1: negative regulation of a select subset of cDCs during homeostatic development, and enhancement of DC maturation.
Dietary fibers are major substrates for maintaining and shaping gut microbiota, but the structural specificity of these fibers for the diversity, structure, and function of gut microbiota are poorly understood. Here, we employed an in vitro sequential batch fecal culture approach to address two ecological questions: 1) whether the chemical complexity of a carbohydrate influences its ability to maintain microbial diversity against high dilution pressure 2) whether substrate structuring or obligate microbe-microbe metabolic interactions (e.g. exchange of amino acids or vitamins) exert more influence on maintained diversity. Sorghum arabinoxylan (SAX, a complex polysaccharide), inulin (a low-complexity oligosaccharide) and their corresponding monosaccharide controls were selected as model carbohydrates. Our results demonstrate that complex carbohydrates stably sustain diverse microbial consortia. Furthermore, other metabolic interactions were less influential in structuring microbial consortia consuming SAX than inulin. Finally, very similar final consortia were enriched on SAX from the same individual's fecal microbiota one month later, suggesting that polysaccharide structure is more influential than stochastic alterations in microbiome composition in governing the outcomes of sequential batch cultivation experiments. These data suggest that carbohydrate structural complexity affords independent niches that structure fermenting microbial consortia, whereas other metabolic interactions govern the composition of communities fermenting simpler carbohydrates.
Ethanol production from food wastes does not only solve environmental issues but also provides renewable biofuels. This study investigated the feasibility of producing ethanol from food wastes at high solids content (35%, w/w). A vacuum recovery system was developed and applied to remove ethanol from fermentation broth to reduce yeast ethanol inhibition. A high concentration of ethanol (144 g/L) was produced by the conventional fermentation of food waste without a vacuum recovery system. When the vacuum recovery is applied to the fermentation process, the ethanol concentration in the fermentation broth was controlled below 100 g/L, thus reducing yeast ethanol inhibition. At the end of the conventional fermentation, the residual glucose in the fermentation broth was 5.7 g/L, indicating incomplete utilization of glucose, while the vacuum fermentation allowed for complete utilization of glucose. The ethanol yield for the vacuum fermentation was found to be 358 g/kg of food waste (dry basis), higher than that for the conventional fermentation at 327 g/kg of food waste (dry basis).
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