Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster.

Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster.
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DOI:
10.1371/journal.ppat.1010826
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发表时间:
2022-09
期刊:
影响因子:
6.7
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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宿主行为变化是感染最明显的影响之一。“病态行为”可能涉及各种症状,包括厌食症,抑郁症和活动水平的改变。在这里,使用实时跟踪和行为分析平台,我们表明,在果蝇中,几种全身性细菌感染会导致身体活动显著增加,并且这种活动增加的程度是一些致命感染中生存时间的预测因子。利用复合菌和D.黑腹免疫和活性突变体,我们表明,增加的活动是由至少两种不同的机制。感染藤黄微球菌(一种革兰氏阳性菌,可通过免疫反应迅速清除)后活性增加,严格要求Toll配体spätzle。相比之下,感染新杀弗朗西丝氏菌(一种不能被免疫应答清除的革兰氏阴性细菌)后活性增加完全独立于Toll和平行IMD途径。细菌感染驱动身体活动增加的多种信号机制的存在意味着这种效应可能是宿主反应的一个重要方面。在感染期间经常观察到病态行为。动物已经被证明会改变它们的进食,交配,社交和休息(睡眠)行为以应对感染。我们在这里表明,感染细菌的果蝇通过增加身体活动和减少睡眠时间来做出反应。这种活性的增加在一些但不是所有的细菌感染中可见,并且似乎是由至少两种不同的机制驱动的:对于一些细菌,激活免疫应答是诱导活性增加的唯一要求,而其他细菌诱导活性增加独立于已知的免疫检测途径。活动增加的生物学作用尚不清楚;野生苍蝇可能被迫逃离感染风险或病原体负担高的地点。或者,增加的活性可以提供不太直接的抗微生物功能。例如,活跃的动物可能更有可能遇到潜在的配偶或食物资源。
Host behavioural changes are among the most apparent effects of infection. ‘Sickness behaviour’ can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here, using a real-time tracking and behavioural profiling platform, we show that in Drosophila melanogaster, several systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in some lethal infections. Using multiple bacteria and D. melanogaster immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with Micrococcus luteus, a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the Toll ligand spätzle. In contrast, increased activity after infection with Francisella novicida, a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of both Toll and the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response. Sickness behaviours are often observed during infection. Animals have been shown to change their feeding, mating, social and resting (sleeping) behaviours in response to infection. We show here that fruit-flies infected with bacteria respond by increasing their physical activity and decreasing the amount of time spent sleeping. This increase in activity is seen in some, but not all, bacterial infections, and appears to be driven by at least two different mechanisms: with some bacteria, activating the immune response is the only requirement to induce increased activity, while other bacteria induce increased activity independently of known immune detection pathways. The biological role of increased activity is unclear; flies in the wild may be driven to flee sites where infection risk or pathogen burden is high. Alternatively, increased activity could serve a less direct anti-microbial function. For example, active animals may be more likely to encounter potential mates or food resource.
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