Laboratory of Cell Biology, Development and Genetics, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
PLoS Genet. 2019 Mar 1;15(3):e1007931. doi: 10.1371/journal.pgen.1007931. eCollection 2019 Mar.
Dipteran insects transmit serious diseases to humans, often in the form of trypanosomatid parasites. To accelerate research in more difficult contexts of dipteran-parasite relationships, we studied the interaction of the model dipteran Drosophila melanogaster and its natural trypanosomatid Herpetomonas muscarum. Parasite infection reduced fecundity but not lifespan in NF-κB/Relish-deficient flies. Gene expression analysis implicated the two NF-κB pathways Toll and Imd as well as STAT signalling. Tissue specific knock-down of key components of these pathways in enterocytes (ECs) and intestinal stem cells (ISCs) influenced initial numbers, infection dynamics and time of clearance. Herpetomonas triggered STAT activation and proliferation of ISCs. Loss of Relish suppressed ISCs, resulting in increased parasite numbers and delayed clearance. Conversely, overexpression of Relish increased ISCs and reduced uptake. Finally, loss of Toll signalling decreased EC numbers and enabled parasite persistence. This network of signalling may represent a general mechanism with which dipteran respond to trypanosomatids.
双翅目昆虫将严重的疾病传播给人类，通常是以原生动物寄生虫的形式。为了加速在更困难的双翅目-寄生虫关系背景下的研究，我们研究了模式双翅目果蝇 Drosophila melanogaster 与其天然原生动物 Herpetomonas muscarum 的相互作用。寄生虫感染降低了 NF-κB/Relish 缺陷型果蝇的繁殖力，但不影响其寿命。基因表达分析表明，Toll 和 Imd 两条 NF-κB 途径以及 STAT 信号通路都参与其中。在肠细胞 (ECs) 和肠干细胞 (ISCs) 中敲低这些途径的关键成分会影响寄生虫的初始数量、感染动态和清除时间。Herpetomonas 触发了 STAT 的激活和 ISCs 的增殖。Relish 的缺失抑制了 ISCs，导致寄生虫数量增加和清除延迟。相反，Relish 的过表达增加了 ISCs，减少了寄生虫的摄入。最后，Toll 信号的缺失减少了 EC 的数量，并使寄生虫得以持续存在。这个信号网络可能代表了双翅目动物对原生动物的一般反应机制。
