A signaling protease required for melanization in Drosophila affects resistance and tolerance of infections.
A signaling protease required for melanization in Drosophila affects resistance and tolerance of infections.
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DOI：
10.1371/journal.pbio.0060305
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发表时间：
2008-12-09
期刊：
影响因子：
9.8
通讯作者：
Schneider DS
中科院分区：
文献类型：
--
作者：
Ayres JS;Schneider DS
生物体进化出两条在感染中存活的途径--它们可以抵抗病原体的生长(抵抗力)，它们可以忍受感染的致病(耐受性)。这两个属性的总和定义了主机的防御能力。通常，对动物防御的研究集中于了解抵抗机制，或者在较小程度上侧重于耐受机制，因此对这两种机制之间的关系了解很少。假设这些性状能够以独立的方式增加、减少或保持不变，我们建议有九种可能的成对排列。在这里，我们展示了通过对编码在果蝇黑化级联中活跃的蛋白酶CG3066的基因进行单一突变，我们观察到了全谱的变化；这些突变的果蝇在受到各种病原体的攻击时，其抵抗力和耐受性表现出增强和降低。这一结果暗示了黑化在对抗微生物感染方面的作用，并表明免疫反应可以通过微生物依赖的方式影响对感染的抵抗力和耐受性。苍蝇通常被描述为具有简单和刻板的免疫反应，其中单一突变会导致简单的二元免疫变化。我们报告了苍蝇免疫反应的复杂程度，这具有强烈的生态影响。我们认为，免疫反应受到进化的高度调节，因为选择改变对一种病原体的抵抗力的防御可能会改变对其他病原体的抵抗力和耐受性。为了加强防御，生物体可以通过降低入侵病原体的适合度来增强其对感染的抵抗力；或者，宿主可以通过减少给定数量的病原体造成的损害来提高其耐受性。黑化是一种免疫反应，与苍蝇和其他无脊椎动物的防御有关。预计它会引起对感染的抵抗力，以及在黑色素产生过程中产生的活性氧物种介导的宿主损害。我们在这里证明，黑化所需基因的丢失会产生令人惊讶的复杂的表型谱，增加和减少对各种微生物的抗性和耐受性。例如，增加对一种病原体的抗药性可以在对另一种病原体的抗药性或耐受性方面产生相应的变化。因此，可能没有产生完美免疫系统的“最佳”解决方案，只有允许苍蝇应对其祖先所面临的致病威胁的平衡。这种平衡需要平衡抗性和耐受性，我们的研究表明，除非我们测量这两种属性对各种病原体的反应，否则我们不能完全理解宿主的防御属性。预测突变将如何影响宿主的免疫反应并非易事。影响苍蝇与一种病原体相互作用的突变可以增加或降低对其他病原体的抵抗力或耐受性。
Organisms evolve two routes to surviving infections—they can resist pathogen growth (resistance) and they can endure the pathogenesis of infection (tolerance). The sum of these two properties together defines the defensive capabilities of the host. Typically, studies of animal defenses focus on either understanding resistance or, to a lesser extent, tolerance mechanisms, thus providing little understanding of the relationship between these two mechanisms. We suggest there are nine possible pairwise permutations of these traits, assuming they can increase, decrease, or remain unchanged in an independent manner. Here we show that by making a single mutation in the gene encoding a protease, CG3066, active in the melanization cascade in Drosophila melanogaster, we observe the full spectrum of changes; these mutant flies show increases and decreases in their resistance and tolerance properties when challenged with a variety of pathogens. This result implicates melanization in fighting microbial infections and shows that an immune response can affect both resistance and tolerance to infections in microbe-dependent ways. The fly is often described as having an unsophisticated and stereotypical immune response where single mutations cause simple binary changes in immunity. We report a level of complexity in the fly's immune response that has strong ecological implications. We suggest that immune responses are highly tuned by evolution, since selection for defenses that alter resistance against one pathogen may change both resistance and tolerance to other pathogens. To boost its defenses, an organism may increase its resistance to infection by reducing the fitness of the invading pathogen; alternatively, the host may increase its tolerance by reducing the damage caused by a given quantity of pathogen. Melanization is an immune response that has been linked to defense in the fly and other invertebrates. It is expected to cause resistance to infection, as well as host damage mediated by reactive oxygen species generated during melanin production. We demonstrate here that the loss of a gene required for melanization produces a surprisingly complex spectrum of phenotypes, increasing and decreasing both resistance and tolerance to a variety of microbes. For example, increasing resistance to one pathogen can produce corresponding changes in either resistance or tolerance to another pathogen. As a result, there is likely no “best” solution that produces a perfect immune system, only an equilibrium that allows the fly to deal with the pathogenic threats that its ancestors have faced. This equilibrium will require the balancing of both resistance and tolerance, and our study demonstrates that we cannot completely understand the defensive properties of a host unless we measure both of these properties in response to a variety of pathogens. It isn't easy to predict how mutations will affect a host's immune response. Mutations that affect the interaction of a fly with one pathogen can increase or decrease resistance or tolerance to other pathogens.
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影响因子：
3.3
作者：
Ayres, Janelle S.;Freitag, Nancy;Schneider, David S.
通讯作者：
Schneider, David S.
影响因子：
1.5
作者：
Gajewski, Kathleen M.;Sorrentino, Richard P.;Schulz, Robert A.
通讯作者：
Schulz, Robert A.
影响因子：
32.4
作者：
Naitza, S;Rossé, C;Reichhart, JM
通讯作者：
Reichhart, JM
DOI：
10.1073/pnas.0602316103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Schwachtje, Jens;Minchin, Peter E. H.;Baldwin, Ian T.
通讯作者：
Baldwin, Ian T.
影响因子：
3.3
作者：
SIMMS, EL;TRIPLETT, J
通讯作者：
TRIPLETT, J