Arefin Badrul, Kucerova Lucie, Krautz Robert, Kranenburg Holger, Parvin Farjana, Theopold Ulrich
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Institute of Neurobiology, University of Münster, Münster, Germany.
PLoS One. 2015 Aug 31;10(8):e0136593. doi: 10.1371/journal.pone.0136593. eCollection 2015.
Apart from their role in cellular immunity via phagocytosis and encapsulation, Drosophila hemocytes release soluble factors such as antimicrobial peptides, and cytokines to induce humoral responses. In addition, they participate in coagulation and wounding, and in development. To assess their role during infection with entomopathogenic nematodes, we depleted plasmatocytes and crystal cells, the two classes of hemocytes present in naïve larvae by expressing proapoptotic proteins in order to produce hemocyte-free (Hml-apo, originally called Hemoless) larvae. Surprisingly, we found that Hml-apo larvae are still resistant to nematode infections. When further elucidating the immune status of Hml-apo larvae, we observe a shift in immune effector pathways including massive lamellocyte differentiation and induction of Toll- as well as repression of imd signaling. This leads to a pro-inflammatory state, characterized by the appearance of melanotic nodules in the hemolymph and to strong developmental defects including pupal lethality and leg defects in escapers. Further analysis suggests that most of the phenotypes we observe in Hml-apo larvae are alleviated by administration of antibiotics and by changing the food source indicating that they are mediated through the microbiota. Biochemical evidence identifies nitric oxide as a key phylogenetically conserved regulator in this process. Finally we show that the nitric oxide donor L-arginine similarly modifies the response against an early stage of tumor development in fly larvae.
除了通过吞噬作用和包囊化在细胞免疫中发挥作用外，果蝇血细胞还释放可溶性因子，如抗菌肽和细胞因子，以诱导体液免疫反应。此外，它们还参与凝血、伤口愈合以及发育过程。为了评估它们在感染昆虫病原线虫期间的作用，我们通过表达促凋亡蛋白来消耗幼稚幼虫中存在的两类血细胞，即浆细胞和晶细胞，以产生无血细胞（Hml-apo，最初称为无血细胞）的幼虫。令人惊讶的是，我们发现Hml-apo幼虫对线虫感染仍具有抗性。在进一步阐明Hml-apo幼虫的免疫状态时，我们观察到免疫效应途径发生了转变，包括大量的片状细胞分化、Toll途径的诱导以及imd信号的抑制。这导致了一种促炎状态，其特征是血淋巴中出现黑色素瘤结节，并导致严重的发育缺陷，包括蛹期致死率和存活个体的腿部缺陷。进一步分析表明，我们在Hml-apo幼虫中观察到的大多数表型可通过施用抗生素和改变食物来源得到缓解，这表明它们是由微生物群介导的。生化证据表明一氧化氮是这一过程中关键的系统发育保守调节因子。最后，我们表明一氧化氮供体L-精氨酸同样会改变果蝇幼虫对肿瘤发育早期阶段的反应。
