MRC Centre for Molecular Bacteriology and Infection and Department of Life Sciences, Imperial College London, London, United Kingdom.
Front Immunol. 2020 Jul 8;11:1419. doi: 10.3389/fimmu.2020.01419. eCollection 2020.
The origins and causes of infection pathologies are often not understood. Despite this, the study of infection and immunity relies heavily on the ability to discern between potential sources of pathology. Work in the fruit fly has supported the assumption that mortality resulting from bacterial invasion is largely due to direct host-pathogen interactions, as lower pathogen loads are often associated with reduced pathology, and bacterial load upon death is predictable. However, the mechanisms through which these interactions bring about host death are complex. Here we show that infection with the bacterium leads to metabolic dysregulation and, using treatment with a bacteriostatic antibiotic, we show that this pathology is the result of direct interaction between host and pathogen. We show that mutants of the immune deficiency immune pathway fail to exhibit similar metabolic dysregulation, supporting the idea that the reallocation of resources for immune-related activities contributes to metabolic dysregulation. Targeted investigation into the cross-talk between immune and metabolic pathways has the potential to illuminate some of this interaction.
感染病理学的起源和原因通常不为人知。尽管如此，感染和免疫的研究仍然非常依赖于辨别潜在病理来源的能力。果蝇的研究支持了这样一种假设，即细菌入侵导致的死亡率在很大程度上是由于直接的宿主-病原体相互作用，因为较低的病原体负荷通常与减少的病理学相关，并且死亡时的细菌负荷是可预测的。然而，这些相互作用导致宿主死亡的机制是复杂的。在这里，我们表明感染细菌会导致代谢失调，并且使用抑菌抗生素治疗，我们表明这种病理学是宿主和病原体之间直接相互作用的结果。我们表明，免疫缺陷免疫途径的突变体不能表现出类似的代谢失调，这支持了这样一种观点，即免疫相关活动的资源重新分配导致代谢失调。对免疫和代谢途径之间的交叉对话进行有针对性的研究有可能阐明其中的一些相互作用。
