Cryptosporidium parvum-specific mucosal immune response in C57BL/6 neonatal and gamma interferon-deficient mice:: Role of tumor necrosis factor alpha in protection
Cryptosporidium parvum-specific mucosal immune response in C57BL/6 neonatal and gamma interferon-deficient mice:: Role of tumor necrosis factor alpha in protection
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DOI：
10.1128/iai.69.3.1635-1642.2001
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发表时间：
2001-03-01
影响因子：
3.1
通讯作者：
Laurent, F
中科院分区：
文献类型：
--
作者：
Lacroix, S;Mancassola, R;Laurent, F
新生小鼠和C57 BL/6 γ干扰素（IFN-γ）敲除（C57 BL/6-GKO）小鼠均对微小隐孢子虫易感，但感染过程不同，新生小鼠能够在3周内清除寄生虫，而C57 BL/6-GKO小鼠根据年龄迅速死亡或保持慢性感染。IFN-γ导致保护性免疫的机制仍然知之甚少，为了研究IFN-γ对C.结果表明，新生小鼠感染后4 d和9 d，IFN-γ mRNA表达迅速上调，而GKO（新生和成年）小鼠感染后9 d，IFN-γ mRNA表达显著上调。在GKO小鼠中，Th1型反应在感染期间发生了显着改变，而Th2型细胞因子白细胞介素4（IL-4）和IL-10的mRNA表达水平在两种小鼠模型中均增加。在没有IFN-γ的情况下，成年敲除小鼠上调了粘膜中炎性细胞因子（如IL-1 β、IL-6和粒细胞-巨噬细胞集落刺激因子）的mRNA水平，但没有上调肿瘤坏死因子α（TNF-α），而所有这些细胞因子在感染的新生小鼠中均上调。进一步的实验表明，将TNF-α注射到GKO成年小鼠中显著减少了卵囊脱落。本研究的结果表明，感染的决议是依赖于在C57 BL/6小鼠的粘膜中的Th1型细胞因子的表达和TNF-α可能参与控制寄生虫的发展。
Both neonatal and C57BL/6 gamma interferon (IFN-gamma) knockout (C57BL/6-GKO) mice are susceptible to Cryptosporidium parvum, but the course of infection is different, Neonatal mice are able to clear the parasite within 3 weeks, whereas C57BL/6-GKO mice, depending on age, die rapidly or remain chronically infected. The mechanism by which IFN-gamma leads to a protective immunity is yet poorly understood, In order to investigate the effect of IFN-gamma on other cytokines expressed in the intestinal mucosa during C. parvum infection, we studied cytokine mRNA expression in the neonates and GKO (neonatal and adult) mice by quantitative reverse transcription-PCR (RT-PCR) at 4 and 9 days after infection, IFN-gamma mRNA levels were quickly and strongly up-regulated in the mucose of neonatal mice. In GKO mice, the Th1-type response was dramatically altered during the infection, whereas the mRNA expression levels of the Th2-type cytokines interleukin 4 (IL-4) and IL-10 were increased in both mouse models. In the absence of IFN-gamma, the adult knockout mice up-regulated the mRNA levels of inflammatory cytokines, such as IL-1 beta, IL-6, and granulocyte-macrophage colony-stimulating factor, in the mucosa, but not tumor necrosis factor alpha (TNF-alpha), whereas all these cytokines were upregulated in the infected neonatal mice. Further experiments indicated that injections of TNF-alpha into GKO adult mice significantly reduced oocyst shedding. The results of the present study indicate that the resolution of infection is dependent on the expression of Th1-type cytokines in the mucosa of C57BL/6 mice and that TNF-alpha may participate in the control of parasite development.