Kinetics of mosquito-injected Plasmodium sporozoites in mice: fewer sporozoites are injected into sporozoite-immunized mice.

Kinetics of mosquito-injected Plasmodium sporozoites in mice: fewer sporozoites are injected into sporozoite-immunized mice.
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DOI:
10.1371/journal.ppat.1000399
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发表时间:
2009-04
期刊:
影响因子:
6.7
通讯作者:
Vanderberg J
Vanderberg J
中科院分区:
医学1区
文献类型:
--
作者:
Kebaier C;Voza T;Vanderberg J

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当蚊子将子孢子引入哺乳动物宿主的皮肤时,疟疾开始。为了成功地继续感染,子孢子必须侵入真皮中的血管并被运送到肝脏。然而,大量的子孢子可能进入皮肤中的淋巴管或在蚊子叮咬后很长时间内留在皮肤中。我们使用荧光显微镜的伯氏疟原虫子孢子表达荧光蛋白,以评估子孢子从皮肤消失的动力学。注射到免疫小鼠的子孢子被迅速固定,似乎没有侵入真皮血管,并在几个小时内变得形态学降解。引人注目的是,蚊子引入免疫小鼠的子孢子明显少于未免疫小鼠,这可能是由于蚊子唾液中的可溶性子孢子抗原与喙尖处的同源宿主抗体之间形成免疫复合物所致。这些结果表明,针对子孢子的保护性抗体可以通过减少注射到免疫宿主中的子孢子的数量和通过抑制注射的子孢子进入真皮血管的运动来起作用。疟疾是由蚊子将疟疾子孢子注射到皮肤中引起的。为了成功地继续感染,子孢子必须侵入皮肤中的血管以运输到肝脏。然而,这些注射的子孢子中的大多数不能到达血液。成功侵入血液的子孢子的数量可能会影响随后的临床疟疾感染的特征。我们通过显微镜研究了由蚊子注射到小鼠体内的啮齿类疟原虫伯氏疟原虫的荧光子孢子。子孢子被引入已经免疫的小鼠体内,变得固定不动,不能到达血液;那些留在叮咬部位的子孢子在几小时内降解。引人注目的是,蚊子将显著更少的子孢子引入免疫小鼠的皮肤中。这些发现表明,针对子孢子的抗体似乎首先通过减少注射到免疫宿主中的子孢子的数量,然后通过抑制注射的子孢子进入血流的运动来起作用。
Malaria is initiated when the mosquito introduces sporozoites into the skin of a mammalian host. To successfully continue the infection, sporozoites must invade blood vessels in the dermis and be transported to the liver. A significant number of sporozoites, however, may enter lymphatic vessels in the skin or remain in the skin long after the mosquito bite. We have used fluorescence microscopy of Plasmodium berghei sporozoites expressing a fluorescent protein to evaluate the kinetics of sporozoite disappearance from the skin. Sporozoites injected into immunized mice were rapidly immobilized, did not appear to invade dermal blood vessels and became morphologically degraded within several hours. Strikingly, mosquitoes introduced significantly fewer sporozoites into immunized than into non-immunized mice, presumably by formation of an immune complex between soluble sporozoite antigens in the mosquito saliva and homologous host antibodies at the proboscis tip. These results indicate that protective antibodies directed against sporozoites may function both by reducing the numbers of sporozoites injected into immunized hosts and by inhibiting the movement of injected sporozoites into dermal blood vessels. Malaria is initiated by a mosquito injecting malaria sporozoites into the skin. To successfully continue the infection, sporozoites must then invade blood vessels in skin for transportation to the liver. However, the majority of these injected sporozoites are unable to reach the blood. The numbers of sporozoites that successfully invade the blood may influence the characteristics of the subsequent clinical malaria infection. We studied this by microscopy with fluorescent sporozoites of the rodent malaria parasite Plasmodium berghei injected into mice by mosquitoes. Sporozoites introduced into mice that have been immunized against sporozoites become immobilized and cannot reach the blood; those that remain at the bite site become degraded within several hours. Strikingly, mosquitoes introduce significantly fewer sporozoites into skin of immunized mice. These findings indicate that antibodies directed against sporozoites seem to function both by reducing the numbers of sporozoites injected into immunized hosts in the first place and then by inhibiting the movement of the injected sporozoites into the bloodstream.
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发表时间: 2006-10-01
影响因子: 4
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