Th1/Th2 cytokine responses of Angiostrongyluscantonensis infected mice

本研究结果如下：1。当敏感株BALB/和耐药株C57BL/6分别感染广东管圆线虫后，它们的脑脊液（CSF）中出现IL-5细胞因子反应，并在感染后12-15天（p.i）达到高峰，提示这是脑脊液嗜酸性粒细胞增多的主要原因。2. 脑脊液中T细胞表达IL-5、IL-4和IL-2 mRNA，但不表达ifn - γ mRNA。4种细胞因子的产生在两种小鼠品系间无显著差异。4. 当BALB/c小鼠在感染广东单胞菌前7-18天感染过corsoestoides时，与单胞菌感染小鼠相比，这些小鼠的发病率较轻，死亡率较低。这可能是由于同时感染corti和can的小鼠在大约30天内虫虫恢复较低所致。M.corti感染小鼠出现Th2显性细胞因子反应，IL-2反应明显高于a .cantonensis感染小鼠。6. 在BALB/c小鼠同时感染corti和广东单胞菌时，观察到的轻微发病率和低死亡率不能用以上4种细胞因子反应来解释。7. 与C3H/HeN对照小鼠相比，IL-5转基因小鼠感染广东a.c anensis后对颅内蠕虫的杀伤速度更快。这些感染IL-5转基因小鼠的脑脊液嗜酸性粒细胞明显高于C3H/HeN小鼠。8. IL-5转基因广州a.b anensis感染小鼠脑膜血管周围及寄生在其蛛网膜下腔的蛔虫周围可见明显的嗜酸性粒细胞浸润。大多数嗜酸性粒细胞被发现是脱颗粒的。9. IL-5受体α基因敲除小鼠感染广东a.c anensis后，颅内蠕虫恢复率明显高于感染杂合子或野生型小鼠。相反，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。这些数据清楚地表明，广东a.c anensis感染小鼠在局部CSF中诱导Th2显性细胞因子反应，特别是IL-5，从而引起显著的CSF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。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