Loch Gerrit, Zinke Ingo, Mori Tetsushi, Carrera Pilar, Schroer Jonas, Takeyama Haruko, Hoch Michael
Molecular Developmental Biology, Life & Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
Molecular Brain Physiology and Behavior, Life & Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
PLoS One. 2017 May 17;12(5):e0176689. doi: 10.1371/journal.pone.0176689. eCollection 2017.
Antimicrobial peptides (AMPs) are important defense molecules of the innate immune system. High levels of AMPs are induced in response to infections to fight pathogens, whereas moderate levels induced by metabolic stress are thought to shape commensal microbial communities at barrier tissues. We expressed single AMPs in adult flies either ubiquitously or in the gut by using the inducible GeneSwitch system to tightly regulate AMP expression. We found that activation of single AMPs, including Drosocin, resulted in a significant extension of Drosophila lifespan. These animals showed reduced activity of immune pathways over lifetime, less intestinal regenerative processes, reduced stress response and a delayed loss of gut barrier integrity. Furthermore, intestinal Drosocin induction protected the animals against infections with the natural Drosophila pathogen Pseudomonas entomophila, whereas a germ-reduced environment prevented the lifespan extending effect of Drosocin. Our study provides new insights into the crosstalk of innate immunity, intestinal homeostasis and ageing.
抗菌肽（AMPs）是先天免疫系统的重要防御分子。感染时会诱导产生高水平的抗菌肽以对抗病原体，而代谢应激诱导产生的中等水平抗菌肽则被认为可塑造屏障组织处的共生微生物群落。我们通过使用可诱导的基因开关系统在成年果蝇中普遍或在肠道中表达单一抗菌肽，以严格调控抗菌肽的表达。我们发现，包括果蝇抗菌肽在内的单一抗菌肽的激活导致果蝇寿命显著延长。这些动物在整个生命周期中免疫途径的活性降低，肠道再生过程减少，应激反应降低，肠道屏障完整性丧失延迟。此外，肠道中果蝇抗菌肽的诱导可保护动物免受天然果蝇病原体嗜昆虫假单胞菌的感染，而无菌环境则阻止了果蝇抗菌肽的寿命延长作用。我们的研究为先天免疫、肠道稳态和衰老之间的相互作用提供了新的见解。
