Th1/Th2 cytokine responses of Angiostrongyluscantonensis infected mice

本研究取得以下结果：1. BALB/c和C57 BL/6分别感染广州管圆线虫后，其脑脊液（CSF）中产生IL-5细胞因子反应，在感染后12-15天（p.i.）提示这是CSF嗜酸性粒细胞增多的主要原因。2. CSF中的T细胞显示IL-5、IL-4和IL-2 mRNA表达，但不显示IFN-γ mRNA。4种细胞因子的产生在两个品系小鼠之间无显著差异。4.当BALB/c小鼠在感染广州管圆线虫前7-18天预先感染柯氏中囊线虫时，这些小鼠与单感染广州管圆线虫的小鼠相比表现出轻微的发病率和较低的死亡率。这可能是由于在感染后30天左右同时感染柯氏支原体和加拿大圆线虫的小鼠中蠕虫回收率较低所致。5. M.corti感染的小鼠产生Th 2优势细胞因子应答，并且还显示出显著的免疫应答。 ...更多信息 与广州管圆线虫感染小鼠相比，IL-2应答更高。6.上述4种细胞因子反应不能解释柯氏支原体和广州管圆线虫同时感染BALB/c小鼠的轻度发病率和低死亡率。7.感染广州管圆线虫的IL-5转基因小鼠比C3 H/HeN对照小鼠更快地杀死颅内蠕虫。这些感染的IL-5转基因小鼠表现出比C3 H/HeN小鼠高得多的CSF嗜酸性粒细胞增多。8.在广州管圆线虫感染的IL-5转基因小鼠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著的嗜酸性粒细胞浸润。发现这些嗜酸性粒细胞大多数脱颗粒。9.感染广州管圆线虫的IL-5受体α基因敲除小鼠显示出比感染的杂合子或野生型小鼠显著更高的颅内蠕虫恢复。感染的IL-5受体敲除小鼠脑脊液嗜酸性粒细胞数极低。这些数据清楚地表明，广州管圆线虫感染的小鼠在局部CSF中诱导Th 2优势细胞因子应答，特别是IL-5，这反过来又引起显著的CSF嗜酸性粒细胞增多。CSF嗜酸性粒细胞参与杀死颅内蠕虫。少

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