A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi chabaudi infection in mice
A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi chabaudi infection in mice
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DOI：
10.1128/iai.67.9.4435-4442.1999
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发表时间：
1999-09-01
影响因子：
3.1
通讯作者：
Langhorne, J
中科院分区：
文献类型：
--
作者：
Li, C;Corraliza, I;Langhorne, J
用夏氏疟原虫（AS株）感染白细胞介素 - 10（IL - 10）不表达（IL - 10（ - / - ））的小鼠，会导致雌性小鼠病情加重，且部分死亡。在感染急性期，雌性IL - 10（ - / - ）小鼠的低血糖、低体温和体重减轻情况明显比雄性基因敲除小鼠以及所有野生型（WT）小鼠更严重。此时，雌性和雄性IL - 10（ - / - ）小鼠产生的γ干扰素（IFN - γ）、肿瘤坏死因子α（TNF - α）和IL - 12p40 mRNA均比相应的野生型小鼠多。通过注射抗IFN - γ抗体使IL - 10（ - / - ）小鼠的IFN - γ失活，或者培育IL - 10（ - / - ）IFN - γ受体（ - / - ）双基因敲除小鼠，可降低死亡率，但不影响体重、体温或血糖水平。数据表明，不依赖IFN - γ的途径可能是夏氏疟原虫疟疾这些病理特征的原因，并且可能是由于寄生虫对TNF - α的直接刺激。由于雄性和雌性基因敲除小鼠产生的炎性细胞因子都比野生型小鼠多，所以雌性小鼠出现的死亡很可能是由于对这些细胞因子反应的性质或程度，而非产生的IFN - γ或TNF - α的量。
Infection of interleukin-10 (IL-10)-nonexpressing (IL-10(-/-)) mice with Plasmodium chabaudi chabaudi (AS) leads to exacerbated pathology in female mice and death in a proportion of them. Hypoglycemia, hypothermia, and loss in body weight were significantly greater in female IL-10(-/-) mice than in male knockout mice and all wild-type (WT) mice during the acute phase of infection. At this time, both female and male IL-10(-/-) mice produced more gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-12p40 mRNA than their respective WT counterparts. Inactivation of IFN-gamma in IL-10(-/-) mice by the injection of anti-IFN-gamma antibodies or by the generation of IL-10(-/-) IFN-gamma receptor(-/-) double-knockout mice resulted in reduced mortality but did not affect body weight, temperature, or blood glucose levels. The data suggest that IFN-gamma-independent pathways may be responsible for these pathological features of P. chabaudi malaria and may be due to direct stimulation of TNF-alpha by the parasite. Since male and female knockout mice both produce more inflammatory cytokines than their WT counterparts, it is likely that the mortality seen in females is due to the nature or magnitude of the response to these cytokines rather than the amount of IFN-gamma or TNF-alpha produced.