Different roles for interleukin-4 during the course of Toxoplasma gondii infection
Different roles for interleukin-4 during the course of Toxoplasma gondii infection
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DOI：
10.1128/iai.64.3.897-904.1996
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发表时间：
1996-03-01
影响因子：
3.1
通讯作者：
Alexander, J
中科院分区：
文献类型：
--
作者：
Roberts, CW;Ferguson, DJP;Alexander, J
比较了白细胞介素4（IL-4）基因敲除（IL-4-/-）小鼠和具有疾病易感遗传背景的野生型（IL-4+/+）小鼠从经口发病至感染后28天的弓形虫感染过程。IL-4缺乏小鼠的死亡率明显高于免疫活性对照组。在整个感染过程中检测的所有时间点，在体外测量的刚第虫特异性脾细胞增殖在组间是相似的，释放到培养上清液中的细胞因子的量不同。在感染后第7天，来自IL-4缺陷小鼠的脾细胞的培养上清液含有比来自IL-4+/+小鼠的脾细胞显著更多的γ干扰素。相反，在感染后第28天，来自野生型小鼠的脾细胞的IL-10产生显著更大。两组小鼠的脾细胞对可溶性速殖子抗原的增殖反应有明显的抑制作用，对伴刀豆球蛋白a的增殖反应在感染后第7 ~ 14天明显降低，对感染后第21 ~ 28天明显增殖。在感染后第28天，脑组织学检查表明IL-4+/+小鼠比IL-4-/-小鼠具有更严重的病理变化和更多的囊肿。此外，虽然在IL-4+/+小鼠的坏死性病变和小胶质细胞结节中存在许多无包囊的单一生物体，但发现很少有无包囊的寄生虫，并且在IL-4缺陷动物中不存在坏死性病变。这些结果表明，在感染的早期急性期观察到的死亡率降低可能是由于IL-4或相关的Th 2衍生产物对促炎细胞因子如γ干扰素的下调作用。然而，IL-4的长期作用是有害的，可能是因为这种细胞因子抑制促炎抗寄生虫产物的能力。这可以解释在IL-4+/+小鼠脑中观察到的寄生虫与包囊的增殖增加。
The course of Toxoplasma gondii infection from initiation of disease perorally until day 28 postinfection was compared between interleukin-4 (IL-4) gene knockout (IL-4-/-) mice and their wild-type (IL-4+/+) counterparts on a disease-susceptible genetic background. The rate of mortality was significantly greater in mice deficient in IL-4 than in the immunocompetent controls, Although levels of T. gondii-specific spleen cell proliferation measured in vitro were similar between groups at all time points examined throughout infection, the quantities of cytokines released into the culture supernatant differed. Culture supernatants from spleen cells derived from IL-4-deficient mice contained significantly more gamma interferon than those derived from IL-4+/+ mice at day 7 postinfection, Conversely, IL-10 production was significantly greater from the spleen cells derived from wild-type mice at day 28 postinfection. Splenocytes from both groups of mice had a marked inhibition of proliferation in response to soluble tachyzoite antigen as well as reduced proliferation in response to concanavalin a between days 7 and 14 postinfection and marked proliferation on days 21 and 28 postinfection. At day 28 postinfection, histological examination of the brains indicated that IL-4+/+ mice had more severe pathological changes and more cysts than IL-4-/- mice. In addition, although many nonencysted single organisms were present in IL-4+/+ mice within both necrotic lesions and microglial nodules, few nonencysted parasites were found, and no necrotic lesions were present in IL-4-deficient animals. These results suggest that the observed reduction in mortality during the early acute phases of infection may be due to the down-regulatory effects of IL-4 or associated Th2-derived products on proinflammatory cytokines such as gamma interferon. However, the long-term effects of IL-4 are detrimental, possibly because of the ability of this cytokine to inhibit proinflammatory antiparasitic products. This may explain the increased parasite multiplication with cysts observed in the brains of IL-4+/+ mice.