Sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites.
Sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites.
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DOI：
10.1371/journal.ppat.1001309
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发表时间：
2011-03
期刊：
影响因子：
6.7
通讯作者：
Reece SE
中科院分区：
文献类型：
--
作者：
Ramiro RS;Alpedrinha J;Carter L;Gardner A;Reece SE
疟疾寄生虫必须在蚊子媒介的血液中经历一轮有性繁殖才能在宿主之间传播。开发一种阻止寄生虫交配的传播阻断干预措施是生物医学的一个主要目标，但如果寄生虫可以通过简单地调整其性别分配策略来补偿，那么其有效性可能会受到影响。最近，进化理论在性别分配中的应用得到了实验的支持，这些实验表明疟原虫会根据感染遗传多样性来调整其性别比例，这与预测的完全一致。理论还预测，寄生虫应调整性别分配，以应对宿主免疫。虽然数据是支持性的，但这一预测背后的假设--宿主免疫反应对雄性和雌性的交配能力有不同的影响--尚未得到测试。在这里，我们将联合收割机实验工作与理论模型相结合，以研究先天免疫因素是否会影响雄性和雌性寄生虫的发育和生育能力，并发展新的理论来预测寄生虫的性别分配策略应如何演变以应对观察到的影响。具体来说，我们表明，活性氮物种损害配子的男性只，但降低生育能力的男性和女性配子。相反，肿瘤坏死因子-α不影响两性配子发生，但损害合子发育。因此，我们的实验表明，免疫因素对每种性别都有复杂的影响，从降低配子母细胞发育成配子的能力，到影响后代的生存能力。我们将这些结果纳入理论，以预测寄生虫性比策略的进化轨迹是如何形成的配子生产，生育力和后代发育的性别差异。我们表明，针对后代发育的医疗干预比针对杀死男性或女性的干预更有可能是“进化证明”。鉴于开发干扰寄生虫交配的医疗干预措施的动力，我们的数据和理论模型具有重要意义。疟疾和相关寄生虫引起人类、家畜和野生动物的一些最严重的传染病。为了传播，这些寄生虫产生雄性和雌性的性阶段，当被蚊子的血餐吸收时，这些性阶段分化成配子并交配。尽管需要开发一种阻断传播的干预措施，但对寄生虫交配策略的进化知之甚少。然而，最近的研究表明，产生正确的雄性和雌性阶段的比例是交配成功的核心。进化理论预测，性别比例会随着各种影响交配成功的因素而调整，包括宿主免疫力。我们通过调查是否普遍存在的免疫因素差异影响男性和女性的生产和生育能力来测试这一理论。我们的实验表明，免疫因素具有复杂的性别特异性影响，从减少配子产生到影响后代的生存能力。我们使用这些结果来产生理论预测这种影响如何塑造寄生虫性别比例策略的进化轨迹。鉴于开发通过阻断寄生虫交配来预防传播的医学干预措施的动力，我们的研究结果具有重要意义。具体来说，我们认为，针对后代发育的医疗干预措施更有可能是“进化证明”比干预措施与性别特异性的影响。
Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction – that host immune responses have differential effects on the mating ability of males and females – have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely to be ‘evolution-proof’ than interventions directed at killing males or females. Given the drive to develop medical interventions that interfere with parasite mating, our data and theoretical models have important implications. Malaria and related parasites cause some of the most serious infectious diseases of humans, domestic animals and wildlife. To be transmitted, these parasites produce male and female sexual stages that differentiate into gametes and mate when taken up in a mosquito blood meal. Despite the need to develop a transmission-blocking intervention, remarkably little is understood about the evolution of parasite mating strategies. However, recent research demonstrates that producing the right ratio of male to female stages is central to mating success. Evolutionary theory predicts that sex ratios are adjusted in line with a variety of factors that affect mating success, including host immunity. We test this theory by investigating whether ubiquitous immune factors differentially affect the production and fertility of males and females. Our experiments demonstrate that immune factors have complex, sex-specific effects, from reducing gamete production to affecting offspring viability. We use these results to generate theory predicting how such effects shape the evolutionary trajectories of parasite sex ratio strategies. Given the drive to develop medical interventions that prevent transmission by blocking parasite mating, our results have important implications. Specifically, we suggest that medical interventions targeting offspring development are more likely to be ‘evolution-proof’ than interventions with sex-specific effects.
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影响因子：
5.5
作者：
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影响因子：
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