SUMMARYNatural killer (NK) cells are an important component of the immediate immune response to infections, including infection by intracellular bacteria. We have investigated recognition of Chlamydia trachomatis (CT) by NK cells and show that these cells are activated to produce interferon (IFN)-g when peripheral blood mononuclear cells (PBMC) are stimulated with CT organisms. Furthermore, infection of epithelial cell lines with CT renders them susceptible to lysis by human NK cells. Susceptibility was observed 18-24 h following infection and required protein synthesis by the infecting chlamydiae, but not by the host cell; heat or UV inactivated chlamydiae did not induce susceptibility to NK cell lysis. CT infection was also shown to decrease the expression of classical and non-classical major histocompatibility complex (MHC) molecules on infected cells, thus allowing recognition by NK cells when combined with an activating signal. A candidate activating signal is MICA/B, which was shown to be expressed constitutively on epithelial cells.
Control of infection by Chlamydia trachomatis usually requires the production of interferon-gamma. Whilst this can be produced by CD4+ and CD8+ T lymphocytes, natural killer (NK) cells are another important source of this cytokine, and are known to be recruited early to the infected genital tract. We show that both IL-12 and IL-18, which synergise to stimulate NK cells to produce interferon-gamma, are produced following the infection of dendritic cells and epithelial cells respectively, since supernatants from infected cells could substitute for recombinant cytokines. These results suggest that conditions, which lead to NK cell production of interferon-gamma will be present at the site of infection, where epithelial cells are the primary targets of infection and dendritic cells within the epithelium can also access the bacterium.
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