Early nonspecific immune responses and immunity to blood-stage nonlethal Plasmodium yoelii malaria

Early nonspecific immune responses and immunity to blood-stage nonlethal Plasmodium yoelii malaria
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DOI:
10.1128/iai.68.11.6127-6132.2000
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发表时间:
2000-11-01
影响因子:
3.1
通讯作者:
De Souza, JB
De Souza, JB
中科院分区:
医学2区
文献类型:
--
作者:
Choudhury, HR;Sheikh, NA;De Souza, JB

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本文研究了自然杀伤细胞(NK)和γ δ T细胞(γ δ T)在约氏疟原虫(Plasmodiumyoelii)非致死性感染后保护性免疫形成中的早期作用。脾脏γ干扰素水平显着增加高于背景免疫缺陷和同窝小鼠感染后24小时。自然杀伤细胞的耗竭导致γ干扰素水平显著降低,寄生虫血症控制不佳,特别是在严重的联合免疫缺陷小鼠中。在同窝仔中,γ干扰素水平部分降低,但寄生虫血症正常消退。然而,在无胸腺小鼠中,自然杀伤细胞耗竭对γ干扰素的产生没有影响。感染后24小时,所有动物的肿瘤坏死因子α水平均升高,自然杀伤细胞耗竭不影响应答。然而,在T细胞耗竭的动物中,γ干扰素和肿瘤坏死因子α水平均在感染后24小时降低,耗竭的小鼠无法控制其寄生虫血症。这些结果表明,这两种细胞因子的早期生产是重要的寄生虫血症的早期控制和自然杀伤细胞和γ δ T细胞同样有助于其生产。这些数据还表明,感染的后续解决需要早期产生γ干扰素,这可能是通过切换适当的T辅助细胞亚群和其他重要的寄生虫毒性效应机制发挥作用。
The early role of natural killer cells and gamma delta T cells in the development of protective immunity to the blood stage of nonlethal Plasmodium yoelii infection was studied, Splenic cytokine levels were measured 24 h after infection of natural killer cell-depleted immunodeficient and littermate mice or transiently T-cell-depleted normal mice. Splenic gamma interferon levels were significantly increased above background in immunodeficient and littermate mice 24 h after infection. Depletion of natural killer cells resulted in markedly depressed gamma interferon levels and poor control of parasitemia, particularly in severe combined immunodeficient mice. In the littermates, gamma interferon levels were partially reduced, but parasitemias were resolved normally. However, in athymic mice, natural killer cell depletion had no effect on gamma interferon production. Levels of tumor necrosis factor alpha were increased in all animals 24 h after infection, and responses were not affected by natural killer cell depletion, However, in T-cell-depleted animals, both gamma interferon and tumor necrosis factor alpha levels were decreased 24 h after infection, and depleted mice were unable to control their parasitemia, These results suggest that the early production of both cytokines is important in the early control of parasitemia and that both natural killer and gamma delta T cells contribute equally towards their production. The data also suggest that the subsequent resolution of infection requires early production of gamma interferon, which might act by switching on the appropriate T-helper-cell subsets and other essential parasitotoxic effector mechanisms.