Natural killer cells contribute to the lethality of a murine model of Escherichia coli infection

Background. Cooperative interactions between natural killer (NK) cells and macrophages occur normally during the course of the early immune response to bacterial, protozoal, and viral pathogens, with each cellular compartment providing the other with critical stimulatory factors. We conducted the present study to determine whether NK cells contribute to the dysregulated immune response that accompanies septic shock. Methods. An analysis of the lethality of Escherichia coli CP9 was conducted in mice that had been depleted of NK cells via the injection of an anti-asialo GM1 antibody and in CD3epsilon transgenic mice that are deficient in both NK cells and T cells. The 2 groups of mice were analyzed for serum levels of interferon-gamma, tumor necrosis factor-alpha, and interleukin-1beta as well as activation of NTkappaB and STAT1, 2 proinflammatory transcription factors. Results. NK cell-depleted and NK cell-deficient mice exhibited 80% survival in the face of an intraperitoneal bacterial challenge, whereas control mice all died within 12 hours. Serum levels of proinflammatory cytokines were markedly reduced in NK-depleted mice. NFkappaB and STAT1 activation were also reduced. NK-depleted mice exhibited less inflammation within multiple organs on histologic analysis. Conclusions. These results show that NK cells may contribute to the lethality of bacterial infections via effects on cytokine production.