|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 2000 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1999 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
The intimate interaction between immune system and nerve system is known to be involved in homeostasis. We studied the orchestra betwwen these two systems in Listeria monocytogenes-infected mouse model in which the sympathetic system, especially noradrenergic nerve terminals, is destroyed by administration of 6-hydroxydopamine (6-OHDA).
(1) When mice was pretreated with 6-OHDA), host defense to L.monocytogenes infection was augmented late in infection. This effect was prevented by pretreatment with desipramine, which blocks the uptake of 6-OHDA into the nerve fibers.
(2) We investigated the effect of denervation by 6-OHDA on phagocytic, listericidal, and NO production by splenic macrophages and peritoneal macrophages. However, activation of either macrophages was not observed.
(3) We investigated the effect of denervation by 6-OHDA on T-cell-dependent antilisterial resistance by depletion of T-cell subsets in vivo. Augmentation of the resistance by denervation was abolished by depletion of CD8 T cells, suggesting that CD8 T cells are involved in this phenomenon.
(4) We investigated the effect of denervation by 6-OHDA on cytokine production by splenic dendritic cells. IL-12, TNF-α and IFN-γ production induce by heat killed L.monocytogenes was augmented, suggesting that IL-12-mediated induction of T-helper 1 polarization by dendritic cells might be involved in augmentation of antilisterial resistance by denervation.
(5) We also investigated the role of adrenergic receptors on host defense to L.monocytogenes infection. Administration of α-adrenergic receptor antagonists, but not β-adrenergic receptor antagonists, inhibited antilisterial resistance, suggesting that α-adrenergic receptors are involved in host defense to L.monocytogenes infection.
Our results demonstrated that the intimate interactions between immune system and nerve system might be required to control L.monocytogenes infection.