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 CD epsilon 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 NFkappaB 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. NF kappaB 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.
Badgwell
Brian
B
Department of Surgery, Arthur G. James Comprehensive Cancer Center, University of Buffalo, NY, USA.
Parihar
Robin
R
Magro
Cynthia
C
Dierksheide
Julie
J
Russo
Thomas
T
Carson
William Edgar
WE
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism; D017252:CD3 Complex; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004927:Escherichia coli Infections / Q000276:immunology* / Q000401:mortality*; D005047:Etoposide / Q000378:metabolism; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology*; D008727:Methotrexate / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D050794:STAT1 Transcription Factor; D018805:Sepsis / Q000276:immunology* / Q000401:mortality*; D013154:Spleen / Q000166:cytology; D015996:Survival Rate; D015534:Trans-Activators / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D017252:CD3 Complex; C115335:CD3E protein, human; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005047:Etoposide; D004317:Doxorubicin; D007371:Interferon-gamma; D003520:Cyclophosphamide; D008727:Methotrexate