Dynamic Changes of Natural Killer Cell Immunophenotypes and Receptors According to the Mortality in the Intra-Abdominal Murine Sepsis Model

Sepsis without direct therapeutic drugs is a serious infectious syndrome that presents strong challenges in innovatively reducing mortality and long-term disabilities/fragilities. Immediate intensive actions at the beginning of sepsis are critical for improving prognosis and preventing multiorgan dysfunctions or complications. However, there is an urgent need to introduce alternative options for patients who are refractory to exhaustive resuscitation based on the survival of sepsis campaigns. Natural killer (NK) cells are the core cellular components of the innate immune system, and balanced NK cell activity (NKA) may play a crucial role in hindering the fatal exacerbation of sepsis. Based on conflicting data on whether NKA is harmful or helpful in the course of sepsis, we evaluated NKA following mortality in a murine intra-abdominal sepsis model by measuring the activating/inhibitory NK receptor (NKR) and CD11b/CD27 subpopulations in the peripheral blood, bone marrow, lymph nodes, spleen, and liver. Several experiments have consistently revealed that NKA, which had been reduced immediately after mild-grade sepsis, surviving until day 7 after cecal ligation and puncture, was significantly restored (upregulation of activating NKR, downregulation of inhibitory NKR, further increment of fully mature cytotoxic NK subsets [CD11bhigh/CD27low] or total NK cells, and higher concentration of granzyme B). However, NKA in high-grade sepsis with early entire mortality after cecal ligation and puncture was continuously suppressed. No sustained post-sepsis surge in interferon-γ was observed in the mild-grade sepsis group. In conclusion, persistent repression of NK cell function is associated with a lethal outcome of sepsis.