Insect respiration has long been thought to be solely dependent on an elaborate tracheal system without assistance from the circulatory system or immune cells^1,2. Here we describe that Drosophila crystal cells—myeloid-like immune cells called haemocytes—control respiration by oxygenating Prophenoloxidase 2 (PPO2) proteins. Crystal cells direct the movement of haemocytes between the trachea of the larval body wall and the circulation to collect oxygen. Aided by copper and a neutral pH, oxygen is trapped in the crystalline structures of PPO2 in crystal cells. Conversely, PPO2 crystals can be dissolved when carbonic anhydrase lowers the intracellular pH and then reassembled into crystals in cellulo by adhering to the trachea. Physiologically, larvae lacking crystal cells or PPO2, or those expressing a copper-binding mutant of PPO2, display hypoxic responses under normoxic conditions and are susceptible to hypoxia. These hypoxic phenotypes can be rescued by hyperoxia, expression of arthropod haemocyanin or prevention of larval burrowing activity to expose their respiratory organs. Thus, we propose that insect immune cells collaborate with the tracheal system to reserve and transport oxygen through the phase transition of PPO2 crystals, facilitating internal oxygen homeostasis in a process that is comparable to vertebrate respiration.

长期以来，昆虫呼吸一直被认为完全依赖于复杂的气管系统，没有循环系统或免疫细胞的帮助 ^1,2 。在这里，我们描述了果蝇晶体细胞（称为血细胞的髓样免疫细胞）通过给酚氧化酶 2 (PPO2) 蛋白供氧来控制呼吸。晶体细胞引导血细胞在幼虫体壁的气管和循环系统之间移动以收集氧气。在铜和中性 pH 值的帮助下，氧气被捕获在晶体细胞中 PPO2 的晶体结构中。相反，当碳酸酐酶降低细胞内pH值时，PPO2晶体可以溶解，然后通过粘附在气管上在纤维素中重新组装成晶体。生理上，缺乏晶体细胞或PPO2的幼虫，或表达PPO2铜结合突变体的幼虫，在常氧条件下表现出缺氧反应，并且容易缺氧。这些缺氧表型可以通过高氧、表达节肢动物血蓝蛋白或防止幼虫挖洞活动暴露其呼吸器官来挽救。因此，我们提出昆虫免疫细胞与气管系统协作，通过 PPO2 晶体的相变来储存和运输氧气，从而促进内部氧稳态，其过程类似于脊椎动物的呼吸。