Råberg Lars
Functional Zoology, Department of Biology, Lund University, Lund, Sweden.
PLoS Biol. 2014 Nov 4;12(11):e1001989. doi: 10.1371/journal.pbio.1001989. eCollection 2014 Nov.
How do we defend ourselves against pathogenic microbes and other parasites infecting us? Research on defence against parasites has traditionally focused on resistance--the ability to prevent infection or limit parasite replication. The genetics, physiology, and evolutionary ecology of such traits are now relatively well understood. During the last few years it has been realized that another, conceptually different type of defence also plays an important role in animal host-parasite interactions. This type of defence is called tolerance, and can be defined as the ability to limit the health effects of parasites without preventing infection or controlling parasite replication. Our understanding of the causes and consequences of variation in tolerance is, however, still rudimentary. Three recent studies shed light on these questions. In a study of HIV in humans, Regoes et al. show that an MHC class I gene affects not only resistance (as previously known) but also tolerance. In a study of voles, Jackson et al. identify a transcription factor mediating age differences in tolerance to macroparasites. Finally, Hayward et al. demonstrate that tolerance to intestinal parasites in sheep is under positive directional selection, but that most of the variation is environmentally induced rather than heritable. These studies increase our knowledge of the genetic and physiological sources of variation in tolerance, and how this variation affects Darwinian fitness. In addition, they illustrate different approaches to untangle tolerance from other factors determining the health effects of infectious disease.
我们如何抵御感染我们的致病微生物和其他寄生虫呢？传统上，针对寄生虫防御的研究主要集中在抗性——预防感染或限制寄生虫繁殖的能力。如今，人们对这类性状的遗传学、生理学及进化生态学已经有了相对深入的了解。在过去几年中，人们认识到，另一种在概念上不同的防御类型在动物宿主与寄生虫的相互作用中也起着重要作用。这种防御类型被称为耐受性，可以定义为在不预防感染或控制寄生虫繁殖的情况下限制寄生虫对健康产生影响的能力。然而，我们对耐受性变异的原因及后果的理解仍然很初步。最近的三项研究为这些问题提供了线索。在一项针对人类艾滋病病毒（HIV）的研究中，雷戈斯等人表明，一种I类主要组织相容性复合体（MHC）基因不仅影响抗性（如之前所知），还影响耐受性。在一项对田鼠的研究中，杰克逊等人确定了一种转录因子，该转录因子介导了对大型寄生虫耐受性的年龄差异。最后，海沃德等人证明，绵羊对肠道寄生虫的耐受性受到正向定向选择，但大多数变异是由环境诱导的，而非遗传的。这些研究增加了我们对耐受性变异的遗传和生理来源的认识，以及这种变异如何影响达尔文适应性。此外，它们还说明了将耐受性与其他决定传染病对健康影响的因素区分开来的不同方法。
