Mesquita Inês, Moreira Diana, Sampaio-Marques Belém, Laforge Mireille, Cordeiro-da-Silva Anabela, Ludovico Paula, Estaquier Jérôme, Silvestre Ricardo
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
ICVS/3Bs-PT Government Associate Laboratory, Guimarães, Braga, Portugal.
Exp Suppl. 2016;107:287-323. doi: 10.1007/978-3-319-43589-3_12.
During host-pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence. Extensive studies have documented the role of AMP-activated protein kinase (AMPK) signaling, a central cellular hub involved in the regulation of energy homeostasis, in host-pathogen interactions. Here, we highlight the most recent advances detailing how pathogens hijack cellular metabolism by suppressing or increasing the activity of the host energy sensor AMPK. We also address the role of lower eukaryote AMPK orthologues in the adaptive process to the host microenvironment and their contribution for pathogen survival, differentiation, and growth. Finally, we review the effects of pharmacological or genetic AMPK modulation on pathogen growth and persistence.
在宿主-病原体相互作用过程中，一系列复杂的事件对于感染的结果至关重要。病原体识别触发强大的细胞信号事件，这些事件转化为针对感染的先天性和适应性宿主免疫的诱导和维持。相反，病原体采用主动机制来操纵宿主细胞调节途径以实现其增殖和存活。其中，病原体对宿主细胞能量代谢的颠覆目前被认为在微生物生长和持续存在中起重要作用。广泛的研究记录了AMP激活的蛋白激酶（AMPK）信号传导（参与能量稳态调节的核心细胞枢纽）在宿主-病原体相互作用中的作用。在这里，我们重点介绍了最新进展，详细说明了病原体如何通过抑制或增加宿主能量传感器AMPK的活性来劫持细胞代谢。我们还讨论了低等真核生物AMPK直系同源物在适应宿主微环境过程中的作用及其对病原体存活、分化和生长的贡献。最后，我们综述了药理学或基因学上对AMPK的调节对病原体生长和持续存在的影响。
