Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, India.
J Cell Physiol. 2014 Aug;229(8):1078-95. doi: 10.1002/jcp.24541.
Systemic immune response via the Immune deficiency pathway requires Drosophila inhibitor of apoptosis protein 2 to activate the NF-κB transcription factor Relish. Malpighian tubules (MTs), simple epithelial tissue, are the primary excretory organs, performing additional role in providing protection to Drosophila against pathogenic infections. MTs hold a strategic position in Drosophila as one of the larval tissues that are carried over to adults, unlike other larval tissues that are histolysed during pupation. In this paper we show that Diap2 is an important regulator of local epithelial immune response in MTs and depletion of Diap2 from MTs, increases susceptibility of flies to infection. In the absence of Diap2, activation and translocation of Relish to the nucleus is abolished and as a consequence the production of IMD pathway dependent AMPs are reduced. Ion channels, (Na(+)/K(+))-ATPase and V-ATPase, are important for the immune response of MTs and expression of AMPs and the IMD pathway genes are impaired on inhibition of transporters, and they restrict the translocation of Relish into the nucleus. We show that Diap2 could be regulating ion channels, as loss of Diap2 consequently reduces the expression of ion channels and affects the balance of ion concentrations which results in reduced uric acid deposition. Thus Diap2 seems to be a key regulator of epithelial immune response in MTs, perhaps by modulating ion channels.
通过免疫缺陷途径的系统性免疫反应需要果蝇凋亡抑制蛋白 2 来激活 NF-κB 转录因子 Relish。马氏管（MTs）是一种简单的上皮组织，是主要的排泄器官，在为果蝇提供对抗病原感染的保护方面发挥额外的作用。MTs 在果蝇中占有战略地位，是幼虫组织中唯一被带到成虫的组织，而其他幼虫组织在蛹化过程中会被组织溶解。在本文中，我们表明 Diap2 是 MTs 中局部上皮免疫反应的重要调节剂，从 MTs 中耗尽 Diap2 会增加果蝇对感染的易感性。在没有 Diap2 的情况下，Relish 的激活和核转位被废除，因此 IMD 途径依赖性 AMP 的产生减少。离子通道（Na(+)/K(+))-ATPase 和 V-ATPase 对 MTs 的免疫反应很重要，AMP 的表达和 IMD 途径基因的表达在转运体抑制剂的作用下受到损害，它们限制 Relish 向核内的转位。我们表明 Diap2 可能调节离子通道，因为 Diap2 的缺失会导致离子通道表达减少，并影响离子浓度的平衡，从而导致尿酸沉积减少。因此，Diap2 似乎是 MTs 中上皮免疫反应的关键调节剂，可能通过调节离子通道。
