Kobler Johanna M, Rodriguez Jimenez Francisco J, Petcu Irina, Grunwald Kadow Ilona C
Neural Circuits and Metabolism, School of Life Sciences, TU Munich, 85354 Freising, Germany; Graduate School of Systemic Neurosciences, LMU Munich, 82152 Martinsried, Germany.
Neural Circuits and Metabolism, School of Life Sciences, TU Munich, 85354 Freising, Germany; ZIEL - Institute for Food and Health, 85354 Freising, Germany.
Curr Biol. 2020 Dec 7;30(23):4693-4709.e3. doi: 10.1016/j.cub.2020.09.022. Epub 2020 Oct 1.
In spite of the positive effects of bacteria on health, certain species are harmful, and therefore, animals must weigh nutritional benefits against negative post-ingestion consequences and adapt their behavior accordingly. Here, we use Drosophila to unravel how the immune system communicates with the brain, enabling avoidance of harmful foods. Using two different known fly pathogens, mildly pathogenic Erwinia carotovora (Ecc15) and highly virulent Pseudomonas entomophila (Pe), we analyzed preference behavior in naive flies and after ingestion of either of these pathogens. Although survival assays confirmed the harmful effect of pathogen ingestion, naive flies preferred the odor of either pathogen to air and also to harmless mutant bacteria, suggesting that flies are not innately repelled by these microbes. By contrast, feeding assays showed that, when given a choice between pathogenic and harmless bacteria, flies-after an initial period of indifference-shifted to a preference for the harmless strain, a behavior that lasted for several hours. Flies lacking synaptic output of the mushroom body (MB), the fly's brain center for associative memory formation, lost the ability to distinguish between pathogenic and harmless bacteria, suggesting this to be an adaptive behavior. Interestingly, this behavior relied on the immune receptors PGRP-LC and -LE and their presence in octopaminergic neurons. We postulate a model wherein pathogen ingestion triggers PGRP signaling in octopaminergic neurons, which in turn relay the information about the harmful food source directly or indirectly to the MB, where an appropriate behavioral output is generated.
尽管细菌对健康有积极影响，但某些种类是有害的，因此，动物必须权衡营养益处与摄入后产生的负面后果，并相应地调整其行为。在此，我们利用果蝇来揭示免疫系统如何与大脑进行沟通，从而实现对有害食物的规避。我们使用两种已知的果蝇病原体，致病性较弱的胡萝卜软腐欧文氏菌（Ecc15）和高致病性的嗜虫假单胞菌（Pe），分析了未接触过病原体的果蝇以及摄入其中任何一种病原体后的偏好行为。尽管生存实验证实了摄入病原体的有害影响，但未接触过病原体的果蝇更喜欢这两种病原体的气味，相较于空气以及无害的突变细菌，这表明果蝇并非天生就对这些微生物产生排斥。相比之下，喂食实验表明，当在致病性细菌和无害细菌之间进行选择时，果蝇在最初的无差异期过后，转而偏好无害菌株，这种行为持续了数小时。缺乏蕈形体（MB）突触输出的果蝇，MB是果蝇大脑中负责联想记忆形成的中心，它们失去了区分致病性细菌和无害细菌的能力，这表明这是一种适应性行为。有趣的是，这种行为依赖于免疫受体PGRP-LC和-LE以及它们在章鱼胺能神经元中的存在。我们提出了一个模型，其中摄入病原体触发章鱼胺能神经元中的PGRP信号传导，进而将有关有害食物来源的信息直接或间接地传递给MB，在MB处产生适当的行为输出。
