In severe liver fibrosis and cirrhosis, failure to control bacterial infection is caused by augmented IFN and IL-10 expression that incapacitates antibacterial immunity of myeloid cells. Targeted interference with the immune regulatory host factors IL-10 and IFN reconstitutes antibacterial immunity and may be used as therapeutic strategy to control bacterial infections in patients with liver cirrhosis.

Virtual memory T (T VM) cells are antigen-naïve CD8 + T cells that exist in a semidifferentiated state and exhibit marked proliferative dysfunction in advanced age. High spare respiratory capacity (SRC) has been proposed as a defining metabolic characteristic of antigen-experienced memory T (T MEM) cells, facilitating rapid functionality and survival. Given the semi-differentiated state of T VM cells and their altered functionality with age, here we investigate T VM cell metabolism and its association with longevity and functionality. Elevated SRC is a feature of T VM , but not T MEM , cells and it increases with age in both subsets. The elevated SRC observed in aged mouse T VM cells and human CD8 + T cells from older individuals is associated with a heightened sensitivity to IL-15. We conclude that elevated SRC is a feature of T VM , but not T MEM , cells, is driven by physiological levels of IL-15, and is not indicative of enhanced functionality in CD8 + T cells.

Nuclear pRelA translocation in hepatocytes Highlights LCMV infection activates NF-jB signaling in hepatocytes. Macrophages, TNFR1 signaling do not induce LCMV-driven hepatocyte NF-jB-activation. Ikkb DHep mice display increased viral infection/replication and lower ISG induction. Ifnar DHep mice recapitulate aberrant virus replication as observed in Ikkb DHep mice. NF-jB signaling is required for efficient ISG induction in HBV-/HDV-infected HepaRG.