The evolution of constitutively active humoral immune defenses in Drosophila populations under high parasite pressure

Both constitutive and inducible immune mechanisms are employed by hosts for defense against infection. Constitutive immunity allows for a faster response, but it comes with an associated cost that is always present. This trade-off between speed and fitness costs leads to the theoretical prediction that constitutive immunity will be favored where parasite exposure is frequent. We selected populations of Drosophila melanogaster under high parasite pressure from the parasitoid wasp Leptopilina boulardi. With RNA sequencing, we found the evolution of resistance in these populations was associated with them developing constitutively active humoral immunity, mediated by the larval fat body. Furthermore, these evolved populations were also able to induce gene expression in response to infection to a greater level, which indicates an overall more activated humoral immune response to parasitization. The anti-parasitoid immune response also relies on the JAK/STAT signaling pathway being activated in muscles following infection, and this induced response was only seen in populations that had evolved under high parasite pressure. We found that the cytokine Upd3, which induces this JAK/STAT response, is being expressed by immature lamellocytes. Furthermore, these immune cells became constitutively present when populations evolved resistance, potentially explaining why they gained the ability to activate JAK/STAT signaling. Thus, under intense parasitism, populations evolved resistance by increasing both constitutive and induced immune defenses, and there is likely an interplay between these two forms of immunity.

宿主可通过组成型免疫与诱导型免疫两种机制抵御病原体感染。组成型免疫能够实现更快的免疫应答，但始终伴随恒定的适合度成本。这种速度与适合度成本之间的权衡关系，在理论上预示：当寄生虫暴露频率较高时，组成型免疫将更具进化优势。我们选取了长期暴露于寄生蜂布氏丽金小蜂（Leptopilina boulardi）高寄生压力下的黑腹果蝇（Drosophila melanogaster）种群。借助RNA测序（RNA sequencing）技术，我们发现这些种群的抗性进化与其发育出组成型活化的体液免疫（humoral immunity）相关，该免疫过程由幼虫脂肪体（fat body）介导。此外，经进化的种群还可在感染后诱导更高水平的基因表达，这提示其针对寄生的体液免疫应答整体处于更为活化的状态。抗寄生蜂的免疫应答还依赖于感染后肌肉组织中激活的JAK/STAT信号通路（JAK/STAT signaling pathway），且这类诱导型应答仅在高寄生压力下进化的种群中得以观测。我们进一步发现，介导该JAK/STAT应答的细胞因子（cytokine）Upd3由未成熟的片层细胞（lamellocytes）表达。当种群进化出抗性后，这些免疫细胞会呈现组成型持续存在的状态，这或许可以解释为何这些种群获得了激活JAK/STAT信号通路的能力。综上，在强烈的寄生选择压力下，果蝇种群通过同时增强组成型与诱导型免疫防御进化出抗性，且这两类免疫形式之间很可能存在相互调控的交互作用。