Molecular mechanism of macrophage activation and intracellular parasitism by intracellular parasitic bacteria

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(1) Listeriolysin 0 (LLO) is the major virulence factor of Listeria monocytogenas a representative intracellular parasitic bacteria, and exhibits a strong cytokine-inducing activity in addition to its role for the escape of this bacterium by cytolytic activity in the host macrophaes. Our study dearly showed that the cytokine-inducing activity, especially gammainterferon-inducing activity is dependent on the N-terminus while the cytolytic activity depends on the C-terminus(2) It was shown that all the cytokine-inducing CDC family proteins including LW filbt activate macrophages far IL-12 and IL-18 and. these macrophage-derived cytokines in turn stimulate NK cells for gamma interferon production that is essential for the induction of Thl-dependent protective immunity(3) There is a significant difference in the cytokine-inducing ability among LLO and allied proteins produced by Listeria seeligeri and Listeria ivanovii. We were able to show that such a difference is highly dependent on the structural difference at the N-terminus domain. A contribution of unique molecule recognizing LLO inside macrophage cytosol was also suggested.(4) Thl cytokine induction by Mycobacterium tuberculosis requires the stimulation with viable bacteria. It was shown that some growing bacteria-derive factor that depends on bacterial metabolism is required.(5) In experimental model of allergic condition in mice, LLO and allied protein with Thl cytokine-inducing activity were effective for the alleviation and control of allergic response.