Biallelic mutations in IRF8 impair human NK cell maturation and function

Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8–/–, but not Irf8+/–, mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense

Production of bacterial cellulose from alternative low-cost substrates

Cellulose is the most widely used biopolymer on Earth. Its large-scale production is mainly from lignocellulosic material (plant origin), however, this plant material is not the only source of this valuable polymer, since microorganisms, like bacteria, naturally produce cellulose, especially those of the genus Komagateibacter (formerly Gluconacetobacter). This type of cellulose is of great interest because of its unique properties such as high purity and resistance, nevertheless, it has not been produced in a large-scale industrial process to date using low-cost substrates, one of the key aspects that should be considered for the industrial obtaining of any biotechnological product. As a main finding we found that the majority of low-cost culture media discussed could have the potential to produce bacterial cellulose on an industrial scale, since in most cases they yield more cellulose (with similar physical chemical characteristics) to those obtained in standard media. However, for an appropriate large-scale production, a specific knowledge about these by-products (since their composition and characteristics, which have a direct impact on the productivity of this biopolymer, are quite heterogeneous) and a proper standardization of them would also be required. Research staff of many industries could use the information presented here to help design a process to use their respective byproducts as substrate to obtain a product with a high added value as bacterial cellulose