Protective role of NK1.1(+) cells in experimental Staphylococcus aureus arthritis

In a model of Staphylococcus aureus-induced septic arthritis in C57Bl/6 mic e we investigated the role of natural killer (NK) cells in the development of disease. Depletion of NK1.1(+) cells was achieved by repeated injections of the PK136 antibody, whereas control mice received an irrelevant monoclo nal antibody, O1C5.B2. Both groups of mice then received injections intrave nously with 2 x 10(7) live S. aureus LS-1 secreting toxic shock syndrome to xin-1 (TSST-1). The mice were evaluated for 16 days with regard to weight, mortality and arthritis. Nine days after bacterial injection, 9/19 mice dep leted of NK cells had developed arthritis compared with 1/17 in the control group (P = 0.01). The experiment was repeated twice with the same outcome. NK cell-depleted and control mice displayed the same degree of histopathol ogical signs of arthritis at day 16. Depletion of NK cells did not affect u ptake of bacteria by phagocytic cells in vitro, or bacterial clearance in v ivo. In NK cell-depleted mice there was a tendency to increased levels of a ntibodies to TSST-1, whereas total immunoglobulin levels were similar to th ose in controls. NK cell depletion of non-infected mice did not affect the magnitude of inflammatory response during the T cell-dependent cutaneous DT H reaction to oxazolone, or during granulocyte-mediated inflammation. Howev er, specific antibody responses to oxazolone were greatly increased in depl eted animals. In conclusion, our study demonstrates that NK cells protect a gainst arthritis during S. aureus infection. This outcome does not seem to be due to an influence on bacterial clearance, but could be due to an inter action with the host anti-inflammatory mechanisms.