Reciprocal virulence and resistance polymorphism in the relationship between Toxoplasma gondii and the house mouse.
Reciprocal virulence and resistance polymorphism in the relationship between Toxoplasma gondii and the house mouse.
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DOI：
10.7554/elife.01298
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发表时间：
2013-10-29
期刊：
影响因子：
7.7
通讯作者：
Howard JC
中科院分区：
文献类型：
--
作者：
Lilue J;Müller UB;Steinfeldt T;Howard JC
在普遍存在的细胞内原生动物弓形虫的天然中间宿主，小鼠的毒力，似乎从进化的角度来看，自相矛盾的，因为小鼠的死亡前包囊中断寄生虫的生命周期。毒性T.弓形虫菌株分泌激酶和假激酶，其与负责小鼠对无毒力菌株的抗性的免疫相关GTP酶（IRG蛋白）结合。这些考虑刺激了对实验室小鼠中未知的IRG等位基因的研究，这些等位基因可能赋予对T.刚地。我们报告说，小鼠IRG系统在野外表现出非凡的多态性复杂性。我们描述了一个IRG单倍型从野生来源的小鼠品系，赋予对有毒的寄生虫的干扰与有毒的激酶复合物的阻力。在这些宿主中，强毒株可以包囊，暗示了T.刚地。http://dx.doi.org/10.7554/eLife.01298.001弓形虫是世界上最常见的寄生虫之一，以其不寻常的生命周期而闻名。它在它的主要宿主猫体内进行有性繁殖，并在粪便中产卵。其他动物，最常见的是啮齿动物，当它们在觅食时不知不觉地吃了鸡蛋时，可能会被感染。一旦进入新的宿主体内，寄生虫就会无性繁殖，直到啮齿动物的免疫系统开始反击。然后，它变成半休眠状态，并在宿主的大脑和肌肉细胞内形成囊肿。另外，这种寄生虫还能使啮齿动物不再害怕猫。这增加了它们被捕获和吃掉的机会，从而帮助寄生虫返回其主要宿主并完成其生命周期。先前的研究表明，T.弓形虫可以通过分泌酶来逃避小鼠的宿主免疫系统，这些酶可以抑制免疫相关蛋白质，称为IRG蛋白。这阻止了感染被清除，并导致宿主在几天内死亡。这些毒力菌株的存在是有趣的，因为杀死宿主从而阻止自身繁殖的寄生虫应该从种群中消除。它们相当普遍的事实表明，一定存在一种迄今为止未知的机制，使啮齿动物能够在这些有毒菌株中生存。Lilue等人现在报道了在野生小鼠品系中存在这种机制。与实验室小鼠相反，野生小鼠产生IRG蛋白，其抑制T.刚地。此外，野生小鼠的IRG基因高度可变，而实验室小鼠几乎都有相同的IRG基因。通过揭示野生小鼠IRG基因的复杂性和变异性，Lilue等人解决了高毒力T。弓形虫菌株可以在小鼠种群中持续存在，并为具有不同毒力水平的寄生虫菌株的进化提供了解释。DOI：http://dx.doi.org/10.7554/eLife.01298.002网站
Virulence in the ubiquitous intracellular protozoon Toxoplasma gondii for its natural intermediate host, the mouse, appears paradoxical from an evolutionary standpoint because death of the mouse before encystment interrupts the parasite life cycle. Virulent T. gondii strains secrete kinases and pseudokinases that inactivate the immunity-related GTPases (IRG proteins) responsible for mouse resistance to avirulent strains. Such considerations stimulated a search for IRG alleles unknown in laboratory mice that might confer resistance to virulent strains of T. gondii. We report that the mouse IRG system shows extraordinary polymorphic complexity in the wild. We describe an IRG haplotype from a wild-derived mouse strain that confers resistance against virulent parasites by interference with the virulent kinase complex. In such hosts virulent strains can encyst, hinting at an explanation for the evolution of virulence polymorphism in T. gondii. DOI: http://dx.doi.org/10.7554/eLife.01298.001 The parasite Toxoplasma gondii is one of the most common parasites worldwide and is known for its unusual life cycle. It reproduces sexually inside its primary host—the cat—and produces eggs that are released in faeces. Other animals, most often rodents, can then become infected when they unknowingly eat the eggs while foraging. Once inside its new host, the parasite reproduces asexually until the rodent’s immune system begins to fight back. It then becomes semi-dormant and forms cysts within the brain and muscle cells of its host. In an added twist, the parasite also causes rodents to lose their fear of cats. This increases their chances of being caught and eaten, thereby helping the parasite to return to its primary host and complete its life cycle. Previous work has shown that virulent strains of T. gondii can evade the host immune system in mice by secreting enzymes that inactivate immune-related proteins called IRG proteins. This prevents the infection being cleared and leads to death of the host within a few days. The existence of these virulent strains is intriguing because parasites that kill their host, and thus prevent their own reproduction, should be eliminated from the population. The fact that they are fairly common suggests that there must be a hitherto unknown mechanism that allows rodents to survive these virulent strains. Lilue et al. now report the existence of such a mechanism in strains of mice found in the wild. In contrast to laboratory mice, wild mice produce IRG proteins that inhibit the enzymes secreted by the virulent strains of T. gondii. Moreover, the IRG genes in wild mice are highly variable, whereas laboratory mice all have virtually identical IRG genes. By uncovering the complexity and variability of IRG genes in wild mice—complexity that has been lost from laboratory strains—Lilue et al. solve the conundrum of how highly virulent T. gondii strains can persist in the mouse population, and offer an explanation for the evolution of parasitic strains with differing levels of virulence. DOI: http://dx.doi.org/10.7554/eLife.01298.002