Neither Mosquito Saliva nor Immunity to Saliva Has a Detectable Effect on the Infectivity of Plasmodium Sporozoites Injected into Mice

Neither Mosquito Saliva nor Immunity to Saliva Has a Detectable Effect on the Infectivity of Plasmodium Sporozoites Injected into Mice
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DOI:
10.1128/iai.00807-09
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发表时间:
2010-01-01
影响因子:
3.1
通讯作者:
Vanderberg, Jerome
Vanderberg, Jerome
中科院分区:
医学2区
文献类型:
--
作者:
Kebaier, Chahnaz;Voza, Tatiana;Vanderberg, Jerome

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当雌性按蚊在寻找血液时,将唾液连同孢子子一起注射到哺乳动物宿主的皮肤中,就会引发疟疾感染。先前的研究表明,唾液可能会增强孢子虫的传染性。使用啮齿动物疟疾模型(伯氏疟原虫和约氏疟原虫),我们无法证明唾液对孢子虫传染性有任何可检测的影响。这对于用洗净的、减毒的恶性疟原虫孢子体对人类进行免疫的计划来说是令人鼓舞的,因为许多人在反复接触蚊子唾液后会出现皮肤过敏反应。如果洗过的孢子体没有明显的传染性丧失,它们的免疫原性可能没有降低;因此,接种者不太可能在尝试用这种孢子虫免疫蚊子唾液时产生皮肤反应。早期的研究还表明,反复接触蚊子唾液会降低蚊子注射到致敏宿主体内的孢子虫的传染性。然而,我们自己的研究表明,小鼠先前暴露于唾液对受感染蚊子传播的孢子虫数量、这些孢子虫从皮肤上消失的速度或孢子虫的传染性没有可检测到的影响。在自然条件下,孢子虫既可传递给可能对蚊子叮咬表现出皮肤过敏的个体,也可传递给可能尚未产生这种反应性的其他人。这是一个诱人的假设,不同个体对蚊子叮咬的反应差异可能会调节孢子虫的传染性,这些孢子虫被传递到皮肤过敏引起的变化环境中。然而,我们的啮齿动物疟疾模型的结果无法支持这样的假设。
Malaria infection is initiated when a female Anopheles mosquito probing for blood injects saliva, together with sporozoites, into the skin of its mammalian host. Prior studies had suggested that saliva may enhance sporozoite infectivity. Using rodent malaria models (Plasmodium berghei and P. yoelii), we were unable to show that saliva had any detectable effect on sporozoite infectivity. This is encouraging for plans to immunize humans with washed, attenuated P. falciparum sporozoites because many individuals develop cutaneous, hypersensitivity reactions to mosquito saliva after repeated exposure. If washed sporozoites have no appreciable loss of infectivity, they likely do not have decreased immunogenicity; thus, vaccinees are unlikely to develop cutaneous reactions against mosquito saliva during attempted immunization with such sporozoites. Earlier studies also suggested that repeated prior exposure to mosquito saliva reduces infectivity of sporozoites injected by mosquitoes into sensitized hosts. However, our own studies show that prior exposure of mice to saliva had no detectable effect on numbers of sporozoites delivered by infected mosquitoes, the rate of disappearance of these sporozoites from the skin or infectivity of the sporozoites. Under natural conditions, sporozoites are delivered both to individuals who may exhibit cutaneous hypersensitivity to mosquito bite and to others who may have not yet developed such reactivity. It was tempting to hypothesize that differences in responsiveness to mosquito bite by different individuals might modulate the infectivity of sporozoites delivered into a milieu of changes induced by cutaneous hypersensitivity. Our results with rodent malaria models, however, were unable to support such a hypothesis.