Jackson Joseph A, Hall Amy J, Friberg Ida M, Ralli Catriona, Lowe Ann, Zawadzka Malgorzata, Turner Andrew K, Stewart Alexander, Birtles Richard J, Paterson Steve, Bradley Janette E, Begon Mike
IBERS, Aberystwyth University, Aberystwyth, United Kingdom.
School of Life Sciences, The University of Nottingham, Nottingham, United Kingdom.
PLoS Biol. 2014 Jul 8;12(7):e1001901. doi: 10.1371/journal.pbio.1001901. eCollection 2014 Jul.
Hosts are likely to respond to parasitic infections by a combination of resistance (expulsion of pathogens) and tolerance (active mitigation of pathology). Of these strategies, the basis of tolerance in animal hosts is relatively poorly understood, with especially little known about how tolerance is manifested in natural populations. We monitored a natural population of field voles using longitudinal and cross-sectional sampling modes and taking measurements on body condition, infection, immune gene expression, and survival. Using analyses stratified by life history stage, we demonstrate a pattern of tolerance to macroparasites in mature compared to immature males. In comparison to immature males, mature males resisted infection less and instead increased investment in body condition in response to accumulating burdens, but at the expense of reduced reproductive effort. We identified expression of the transcription factor Gata3 (a mediator of Th2 immunity) as an immunological biomarker of this tolerance response. Time series data for individual animals suggested that macroparasite infections gave rise to increased expression of Gata3, which gave rise to improved body condition and enhanced survival as hosts aged. These findings provide a clear and unexpected insight into tolerance responses (and their life history sequelae) in a natural vertebrate population. The demonstration that such responses (potentially promoting parasite transmission) can move from resistance to tolerance through the course of an individual's lifetime emphasises the need to incorporate them into our understanding of the dynamics and risk of infection in the natural environment. Moreover, the identification of Gata3 as a marker of tolerance to macroparasites raises important new questions regarding the role of Th2 immunity and the mechanistic nature of the tolerance response itself. A more manipulative, experimental approach is likely to be valuable in elaborating this further.
宿主可能会通过抗性（病原体排出）和耐受性（主动减轻病理症状）相结合的方式来应对寄生虫感染。在这些策略中，动物宿主耐受性的基础相对了解较少，对于其在自然种群中的表现更是知之甚少。我们采用纵向和横断面抽样模式监测了田鼠的自然种群，并对身体状况、感染情况、免疫基因表达和存活率进行了测量。通过按生命史阶段分层的分析，我们证明了成熟雄性田鼠对大型寄生虫的耐受性模式，与未成熟雄性相比，成熟雄性抵抗感染的能力较弱，而是随着负担的积累增加对身体状况的投入，但代价是生殖努力减少。我们确定转录因子Gata3（Th2免疫的介质）的表达是这种耐受性反应的免疫生物标志物。个体动物的时间序列数据表明，大型寄生虫感染导致Gata3表达增加，随着宿主年龄增长，这导致身体状况改善和存活率提高。这些发现为自然脊椎动物种群中的耐受性反应（及其生命史后遗症）提供了清晰且出乎意料的见解。这种反应（可能促进寄生虫传播）在个体一生中从抗性转变为耐受性的证明强调了将其纳入我们对自然环境中感染动态和风险理解的必要性。此外，将Gata3鉴定为对大型寄生虫耐受性的标志物，引发了关于Th2免疫的作用以及耐受性反应本身的机制性质的重要新问题。一种更具操作性的实验方法可能对进一步阐述这一点很有价值。
