Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.
Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.
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DOI：
10.1371/journal.pbio.1000525
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发表时间：
2010-10-19
期刊：
影响因子：
9.8
通讯作者：
Allen JE
中科院分区：
文献类型：
--
作者：
Babayan SA;Read AF;Lawrence RA;Bain O;Allen JE
在幼虫发育过程中，丝虫调整其终身生殖策略，以确定宿主抗性和实验疫苗效力的抗寄生虫免疫细胞的存在。人类和其他哺乳动物对蠕虫寄生虫发起了强有力的免疫攻击，但有有趣的报道称，免疫反应可以增强而不是削弱寄生虫的发育。据推测，蠕虫，像许多自由生活的有机体，应优化其发展和繁殖的线索预测未来的预期寿命。然而，蠕虫寄生虫的免疫依赖性发育迄今为止还没有得到这样的进化解释。通过操纵实验宿主的免疫反应的各个臂，我们表明，丝虫线虫，负责使人类衰弱的疾病，如河盲症和象皮病的寄生虫，加速它们的发展，以响应IL-5驱动的嗜酸性粒细胞增多症，他们感染宿主时遇到的。因此，它们更早、更大量地产生微丝蚴及其传播阶段。嗜酸性粒细胞增多症是丝虫预期寿命的主要宿主决定因素，在幼虫和成虫晚期在解剖学和时间上分开的位置起作用，并且与疫苗介导的保护有关。因此，丝状线虫能够根据进化理论提出的生存概率的环境预测因子来调整它们的繁殖时间表，从而减轻蠕虫最容易受到的免疫攻击的影响。增强对丝虫线虫的保护性免疫，例如通过接种疫苗，在减少传播方面可能不如预期有效，在最坏的情况下，可能导致传播增加，从而导致病理学。许多生物体能够适应他们的发展，他们的环境的严重性的基础上特定的线索，我们已经确定了这样一种现象，称为表型可塑性，在丝虫寄生虫Litomosoides sigmodontis。丝虫感染了全世界约2亿人，人们正在努力寻找一种疫苗来补充目前的药物治疗。虽然抗丝虫免疫可以实现，我们表明，在进化理论的雅阁，当这些寄生虫感染一个新的主机，他们能够调整自己的发展和繁殖的存在下，专门在抗蠕虫攻击的免疫细胞。这些发育时间表在数小时内决定，并影响他们的终身生殖策略;当免疫攻击很强时，死亡率可能很高，他们会更早地产生后代，数量更多。由于目前的实验性疫苗依赖于这些线虫调节其发育的免疫元件，因此它们的表型可塑性可能会减轻接种疫苗人群中疾病负担的预期减少。
During larval development, filarial nematodes adjust their lifelong reproductive strategy to the presence of anti-parasitic immune cells that determine host resistance and experimental vaccine efficacy. Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependant development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology. Many organisms are able to adapt their development to the severity of their environment based on specific cues, and we have identified such a phenomenon, termed phenotypic plasticity, in the filarial parasite Litomosoides sigmodontis. Filarial nematodes infect about 200 million people worldwide, and much effort is going into finding a vaccine that would complement current drug treatments. Although anti-filarial immunity can be achieved, we show, in accord with evolutionary theory, that when these parasites infect a new host, they are able to adjust their development and reproduction to the presence of immune cells specialized in anti-helminth attack. These developmental schedules are determined within hours and impact their lifelong reproductive strategy; when immune attack is strong, and thus mortality is likely to be high, they produce offspring earlier and in greater numbers. Because current experimental vaccines rely on the very immune elements to which these nematodes adjust their development, their phenotypic plasticity could mitigate the expected reduction of disease burden in vaccinated populations.
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