Bench-to-bedside review: Natural killer cells in sepsis - guilty or not guilty?

Bacterial sepsis and septic shock are complex inflammatory disorders associated with a systemic inflammatory response syndrome. In the most severe cases of infection, an overzealous release of proinflammatory cytokines and inflammatory mediators by activated leukocytes, epithelial cells and endothelial cells, known as a 'cytokine storm', leads to deleterious effects such as organ dysfunction and even death. By the end of the 20th century, natural killer (NK) cells were for the first time identified as important players during sepsis. The role of this cell type was, however, double-edged, either 'angel' or 'devil' depending upon the bacterial infection model under study. Bacterial sensors (such as Toll-like receptors) have recently been shown to be expressed at the protein level in these cells. In addition, NK cells are important sources of interferon-gamma and granulocyte-macrophage colony-stimulating factor, which are pro-inflammatory cytokines necessary to fight infection but can contribute to deleterious inflammation as well. Interestingly, an adaptative response occurs aimed to silence them, similar to the well-known phenomenon of endotoxin reprogramming.