Th1/Th2 cytokine responses of Angiostrongyluscantonensis infected mice

广州管圆线虫感染小鼠的Th1/Th2细胞因子反应

• 批准号: 06670251
• 负责人: YOSHIMURA Kentaro
• 金额: $ 1.34万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670251/
• 关键词: Angiostrongylus cantonensis; Mesocestoides corti; eosinophil; Th1 cytokine; Th2 cytokine; RT-PCR; IL-5 transgenic mice; IL-5 receptor alpha knockout mice; IL‐5 transgenic mouse; IL‐5 receptor α knockout mouse; 髄液; マウス; Th1; Th2; IL-5; IL-4

This study yielded the following results : 1. When BALB/cand C57BL/6, susceptible and resistant strains respectively, were infected with Angiostrongylus cantonensis, they developed IL-5 cytokine responses in their cerebrospinal fluid (CSF) with a peak response at days 12-15 postinfection (p.i.), suggesting this being the major cause of CSF eosinophilia. 2. T cells in CSF showed IL-5, IL-4, and IL-2 mRNA expressions but not IFN-gamma mRNA.3. There was no significant differencein production of the 4 kinds of cytokines between two mouse strains. 4. When BALB/c mice were previously infected with Mesocestoides corti 7-18 days prior to A.cantonensis infection, these mice showed mild morbidity and low mortality as compared with mice with monoinfection with A.cantonensis. This might be caused by the low worm recovery in the mice concurrently infected with M.corti and A.can tonensis at around 30 days p.i. 5. M.corti infected mice developed Th2 dominant cytokine responses and also showed a signi … More ficantly higher IL-2 response than A.cantonensis infected mice. 6. Mild morbidity and low mortality observed in BALB/c mice concurrentlyinfected with M.corti and A.cantonensis can not be explained by the above 4 kinds of cytokine responses. 7. IL-5 transgenic mice infected with A.cantonensis killed the intracranial worms more rapidly than C3H/HeN control mice. These infected IL-5 transgenic mice showed much higher CSF eosinophilia than C3H/HeN mice. 8. Prominent eosinophil infiltration was noted around the blood vessels in the meninges of A.cantonensis infected IL-5 transgenic mice and also around the worms parasitizing in their subarachnoid spaces. Most of these eosinophils were found degranulated. 9. IL-5 receptor alpha gene knockout mice infected with A.cantonensis showed a significantly higher intracranial worm recovery than infected heterozygous or wild-type mice. Contrarily, the infected IL-5 receptor knockout mice showed extremely low CSF eosinophilia. These data clearly indicate that A.cantonensis infected mice induce Th2 dominant cytokine responses, especially IL-5, in the local CSF,which in turn evoke prominent CSF eosinophilia. CSF eosinophils are then involved in the killing of intracranial worms. Less

本研究得出以下结果： 1. 当 BALB/can 和 C57BL/6（分别为敏感株和耐药株）感染广州管圆线虫时，它们在脑脊液（CSF）中产生 IL-5 细胞因子反应，并在感染后 12-15 天（p.i.）达到峰值，表明这是 CSF 嗜酸性粒细胞增多的主要原因。 2.脑脊液中的T细胞显示IL-5、IL-4和IL-2 mRNA表达，但不表达IFN-γ mRNA。3．两品系小鼠4种细胞因子的产生量无显着差异。 4.当BALB/c小鼠在感染广州放线虫前7-18天预先感染柯氏中绦虫时，与单独感染广州放线虫的小鼠相比，这些小鼠表现出轻微的发病率和较低的死亡率。这可能是由于在注射后 30 天左右同时感染 M.corti 和 A.can tonsis 的小鼠中蠕虫回收率较低所致。 5. M.corti 感染的小鼠产生了 Th2 主导的细胞因子反应，并且还表现出比 A.cantonensis 感染的小鼠显着更高的 IL-2 反应。 6.同时感染M.corti和A.cantonensis的BALB/c小鼠中观察到的轻度发病率和低死亡率不能用上述4种细胞因子反应来解释。 7.感染广州曲霉的IL-5转基因小鼠比C3H/HeN对照小鼠更快地杀死颅内蠕虫。这些受感染的 IL-5 转基因小鼠表现出比 C3H/HeN 小鼠更高的脑脊液嗜酸性粒细胞增多。 8.在感染IL-5转基因小鼠的脑膜血管周围以及寄生在其蛛网膜下腔的蠕虫周围观察到显着的嗜酸性粒细胞浸润。发现这些嗜酸性粒细胞大部分脱颗粒。 9. 感染广州曲霉的IL-5受体α基因敲除小鼠的颅内蠕虫恢复率明显高于感染的杂合子或野生型小鼠。相反，被感染的IL-5受体敲除小鼠表现出极低的脑脊液嗜酸性粒细胞增多。这些数据清楚地表明，广州曲霉感染的小鼠在局部脑脊液中诱导Th2主导的细胞因子反应，尤其是IL-5，进而引起显着的脑脊液嗜酸性粒细胞增多。然后脑脊液嗜酸性粒细胞参与杀死颅内蠕虫。较少的

项目成果

Yoshimura, K.: "Eosinophils intravenously transferred into Angiostrongylus cantonensis infected nude mice kill intracranial worms in vivo." Acta Parasitol.Turcica. (in press). (1996)

Yoshimura, K.：“将嗜酸性粒细胞静脉注射到感染广州管圆线虫的裸鼠体内，可杀死体内的颅内蠕虫。”

Yoshimura,K.: "Eosinophils intravenously transferred into Angiostrongylus cantonensis infected nude mice kill intracranial worms in vivo." Acta Parasitol.Turcica. (印刷中). (1996)

Yoshimura, K.：“将嗜酸性粒细胞静脉注射到感染广州管圆线虫的裸鼠体内可杀死体内的寄生虫。”（正在出版）。

Sugaya,H.: "Angiostrongylus cantonensis infection in IL-5 transgenic mice and adhesion molecule expressions in their eosinophils harvested from the blood and cerebrospinal fluid." (発表予定).

Sugaya, H.：“IL-5 转基因小鼠中的广州管圆线虫感染及其从血液和脑脊液中采集的嗜酸性粒细胞中的粘附分子表达。”

Sugaya, H.: "Th1 and Th2 cytokine responses in BALB/c and C57BL/6 mice infected with Angiostrongylus cantonensis." (to be published).

Sugaya, H.：“感染广州管圆线虫的 BALB/c 和 C57BL/6 小鼠的 Th1 和 Th2 细胞因子反应。”

吉村堅太郎: "広東住血線虫症における好酸球の役割" 寄生虫誌. 43(補). 41-44 (1994)

Kentaro Yoshimura：“嗜酸性粒细胞在广东血吸虫病中的作用”寄生虫学杂志 43（增刊）41-44（1994）。