Interferon-gamma inhibits the intrahepatocytic development of malaria parasites in vitro.
Interferon-gamma inhibits the intrahepatocytic development of malaria parasites in vitro.
复制标题
干扰素-γ 在体外抑制疟疾寄生虫的肝细胞内发育。
作者：
L. Schofield;A. Ferreira;R. Altszuler;V. Nussenzweig;R. Nussenzweig
在这项研究中，我们研究了重组干扰素（IFN）-γ对伯氏疟原虫外红细胞形式（EEF）在体外生长的高度分化的人肝癌细胞系HEPG 2的活动。我们使用伯氏疟原虫特异性DNA探针通过DNA杂交测定IFN-γ对寄生虫生长的影响。IFN-γ对EEF的特异性活性非常高，并且取决于淋巴因子添加的时间。当IFN-γ加入到含有细胞内EEF的HEPG 2细胞中时，子孢子侵入后6小时，寄生虫DNA复制在10（3）U/ml时被抑制约75%，在1 U/ml时被抑制50%。这种治疗可以消除或大大降低EEF对小鼠的感染性。当在子孢子入侵完成后3小时较早加入时，IFN-γ抑制寄生虫复制的程度甚至更大。当在子孢子侵入前6小时加入IFN-γ时，获得最高水平的抑制（10（2）U/ml时100%抑制，0.1 U/ml时约55%抑制，0.001 U/ml时17%抑制）。我们发现HEPG 2细胞表达大约44，000种IFN-γ的表面受体。这些数据与IFN-γ通过与肝细胞表面受体结合并诱导不利于寄生虫发育的细胞内变化来发挥其抗疟活性的观点一致。色氨酸饥饿似乎不参与这一过程。这些发现也支持这样的想法，即IFN-γ，从免疫T细胞遇到子孢子抗原后释放，可能是一个重要的效应机制，在无菌免疫子孢子的挑战。
In this study, we examined the activity of recombinant interferon (IFN)-gamma against Plasmodium berghei exoerythrocytic forms (EEF) grown in vitro within the highly differentiated human hepatoma cell line HEPG2. We assayed the effect of IFN-gamma on parasite growth by DNA hybridization using a P. berghei specific DNA probe. The specific activity of IFN-gamma against EEF is very high, and depends upon the time of lymphokine addition. When IFN-gamma is added to HEPG2 cells containing intracellular EEF, 6 hr after sporozoite invasion, parasite DNA replication is inhibited by approximately 75% at 10(3) U/ml and 50% at 1 U/ml. This treatment can either abolish or greatly reduce the infectivity of EEF for mice. When added earlier, 3 hr after completion of sporozoite invasion, IFN-gamma inhibits parasite replication to an even greater degree. The highest levels of inhibition were obtained when IFN-gamma was added 6 hr prior to sporozoite invasion (100% inhibition at 10(2) U/ml, approximately 55% inhibition at 0.1 U/ml, and 17% inhibition at 0.001 U/ml). We found that HEPG2 cells express approximately 44,000 surface receptors for IFN-gamma. These data are consistent with the view that IFN-gamma exerts its antimalarial activity by binding to surface receptors on hepatocytes and inducing intracellular changes unfavorable for parasite development. Tryptophan starvation does not appear to be involved in this process. These findings also support the idea that IFN-gamma, released from immune T cells upon encountering sporozoite antigen, may be an important effector mechanism in sterile immunity to sporozoite challenge.