Protective role of NK1.1+ cells in experimentalStaphylococcus aureusarthritis

Abstract

SUMMARYIn a model of Staphylococcus aureus-induced septic arthritis in C57Bl/6 mice we investigated the role of natural killer (NK) cells in the development of disease. Depletion of NK1.1 þ cells was achieved by repeated injections of the PK136 antibody, whereas control mice received an irrelevant monoclonal antibody, O1C5.B2. Both groups of mice then received injections intravenously with 2 × 10 7 live S. aureus LS-1 secreting toxic shock syndrome toxin-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 depleted of NK cells had developed arthritis compared with 1/17 in the control group (P ¼ 0·01). The experiment was repeated twice with the same outcome. NK cell-depleted and control mice displayed the same degree of histopathological signs of arthritis at day 16. Depletion of NK cells did not affect uptake of bacteria by phagocytic cells in vitro, or bacterial clearance in vivo. In NK cell-depleted mice there was a tendency to increased levels of antibodies to TSST-1, whereas total immunoglobulin levels were similar to those in controls. NK cell depletion of non-infected mice did not affect the magnitude of inflammatory response during the T cell-dependent cutaneous DTH reaction to oxazolone, or during granulocyte-mediated inflammation. However, specific antibody responses to oxazolone were greatly increased in depleted animals. In conclusion, our study demonstrates that NK cells protect against 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 interaction with the host anti-inflammatory mechanisms.

Influenza Infection Leads to Increased Susceptibility to Subsequent Bacterial Superinfection by Impairing NK Cell Responses in the Lung

“…Indeed, different from the study by Sun and Metzger, we detected a minimum level of IFN-g in flu-infected lung after S. aureus superinfection (data not shown). Furthermore, to date, NK cells have only been found to contribute to host defense against primary staphylococcal infection (16,34). In contrast, although exaggerated IL-10 responses to streptococcal superinfection in the fluinfected lung was reportedly linked to increased susceptibility (22,35), we did not detect any measurable levels of IL-10 responses to staphylococcal superinfection in the flu-infected lung (data not shown).…”

Natural Killer (NK) Cells in Antibacterial Innate Immunity: Angels or Devils?

“…The protective role of NK cells was also demonstrated in models of infection with different strains of Salmonella (196)(197)(198). Similarly, NK cells were shown to play a critical protective role against S. aureus in septic arthritis and pulmonary models of infection (199,200). In the later case, an elegant study revealed that H1N1 influenza virus infection leads to weakened NK cell activity, particularly in terms of TNF-α production, rendering the host more susceptible to a secondary lung infection by S. aureus (201).…”

Activation of Human NK Cells by Staphylococci and Lactobacilli Requires Cell Contact-Dependent Costimulation by Autologous Monocytes

“…There is increasing evidence that NK cell activation is regulated by the balance between inhibitory and activating signals. In addition, contact-based costimulatory signals derived from activated monocytes, dendritic cells (19), or NKT cells (5) seem to be necessary for early IFN-␥ secretion and thus an appropriate protective innate response in the absence of antigen (46). This in turn may profoundly influence the nature of the adaptive immune response.…”