Apoptosis in Hemocytes Induces a Shift in Effector Mechanisms in the Drosophila Immune System and Leads to a Pro-Inflammatory State.
Apoptosis in Hemocytes Induces a Shift in Effector Mechanisms in the Drosophila Immune System and Leads to a Pro-Inflammatory State.
复制标题
DOI：
10.1371/journal.pone.0136593
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Theopold U
中科院分区：
文献类型：
--
作者：
Arefin B;Kucerova L;Krautz R;Kranenburg H;Parvin F;Theopold U
除了通过吞噬和包被作用于细胞免疫外，果蝇血细胞还释放可溶性因子，如抗菌肽和细胞因子，以诱导体液反应。此外，它们还参与凝血、损伤和发育。为了评估它们在昆虫病原线虫感染过程中的作用，我们通过表达促凋亡蛋白来减少naïve幼虫中存在的两类血细胞浆细胞和晶体细胞，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幼虫仍然对线虫感染有抵抗力。当进一步阐明Hml-apo幼虫的免疫状态时，我们观察到免疫效应途径的转变，包括大量板层细胞分化和诱导Toll-以及imd信号的抑制。这导致促炎状态，其特征是在血淋巴中出现黑色结节，并导致严重的发育缺陷，包括蛹致命性和逃跑者的腿缺陷。进一步的分析表明，我们在Hml-apo幼虫中观察到的大多数表型都可以通过施用抗生素和改变食物来源来缓解，这表明它们是通过微生物群介导的。生化证据表明，一氧化氮在这一过程中是一个关键的系统发育保守调节剂。最后，我们发现一氧化氮供体l -精氨酸类似地改变了果蝇幼虫对早期肿瘤发展的反应。
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.