The control of bacterial infectious diseases by the orchestra of immune system and nerve system

免疫系统和神经系统的管弦乐队控制细菌感染性疾病

• 批准号: 10670247
• 负责人: NAKANE Akio
• 金额: $ 2.11万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670247/
• 关键词: Listeria monocytogenes; Sympathetic nerve; Host defense; IL-12; IFN-γ; TNF-α; Norepinephrine; Adrenergic receptor; マウス; 特異免疫応答; マクロファージ

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.

免疫系统和神经系统之间的密切相互作用参与了体内平衡。我们在单核细胞增生李斯特菌感染小鼠模型中研究了这两个系统之间的相互作用，在该模型中，交感神经系统，特别是去甲肾上腺素能神经末梢被6-羟基多巴胺（6-OHDA）破坏。(1)小鼠经6-OHDA预处理后，在感染后期，宿主对单核细胞增多杆菌感染的防御能力增强。用地西帕明预处理可以阻止6-羟色胺进入神经纤维。(2)我们研究了6-OHDA去神经对脾巨噬细胞和腹膜巨噬细胞吞噬、杀李斯特菌和NO产生的影响。然而，两种巨噬细胞均未被激活。(3)我们通过体内t细胞亚群的消耗研究了6-OHDA去神经支配对t细胞依赖性抗李斯特菌耐药的影响。去神经支配增强的抵抗被CD8 T细胞的耗竭所消除，这表明CD8 T细胞参与了这一现象。(4)研究了6-OHDA去神经对脾树突状细胞产生细胞因子的影响。热杀伤单核增生李斯特菌诱导IL-12、TNF-α和IFN-γ的产生增加，提示IL-12介导的树突状细胞诱导t -辅助性1极化可能参与了去神经支配增强抗李斯特菌抗性的过程。(5)我们还研究了肾上腺素能受体在宿主防御单核细胞增生杆菌感染中的作用。α-肾上腺素能受体拮抗剂而非β-肾上腺素能受体拮抗剂可抑制抗李斯特菌耐药性，提示α-肾上腺素能受体参与宿主对单核细胞增生杆菌感染的防御。我们的研究结果表明，免疫系统和神经系统之间的密切相互作用可能需要控制单核细胞增多杆菌感染。

项目成果

Nakane, A., K.Yamada, S.Hasegawa, D.Mizuki, M.Mizuki, S.Sasaki, and T.Miura.: "Endogenous cytokines during a lethal infection with Listeria monocytogenes in mice."FEMS Microbiology Letters. 175(1). 133-142 (1999)

Nakane, A.、K.Yamada、S.Hasekawa、D.Mizuki、M.Mizuki、S.Sasaki 和 T.Miura.：“小鼠单核细胞增多性李斯特菌致命感染期间的内源性细胞因子。”FEMS 微生物学快报。

D.Mizuki: "Interference between host resistance to Listeria monocytogenes infection and ovalbumin-induced allergic responses in mice"Infection and Immunity. 69・3. 335-341 (2001)

D. Mizuki：“小鼠对单核细胞增多性李斯特菌感染的宿主抵抗力与卵白蛋白诱导的过敏反应之间的干扰”感染与免疫69・3（2001）。

Sasaki, S., S.Nishikawa, T.Miura, M.Mizuki, K.Yamada, H.Madarame, and A.Nakane.: "Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon."Infection and Immunity. 68(5). 24

Sasaki, S.、S.Nishikawa、T.Miura、M.Mizuki、K.Yamada、H.Madarame 和 A.Nakane.：“Interleukin-4 和 interleukin-10 通过调节参与宿主对金黄色葡萄球菌感染的抵抗

S.Sasaki: "Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon"Infection and Immunity. 68・5. 2424-2430 (2000)

S.Sasaki：“白细胞介素 4 和白细胞介素 10 通过调节γ干扰素参与宿主对金黄色葡萄球菌感染的抵抗”感染和免疫 68・5 (2000)。

T.Miura: "Roles of endogenous cytokines in liver apoptosis of mice in lethal Listeria monocytogenes infection"FEMS Immunology and Medical Microbiology. 28・4. 1883-1888 (2000)

T.Miura：“内源性细胞因子在致死性单核细胞增多性李斯特菌感染中小鼠肝脏细胞凋亡中的作用”FEMS 免疫学和医学微生物学 1883-1888（2000）。