Transcriptional host–pathogen responses of <i>Pseudogymnoascus destructans</i> and three species of bats with white-nose syndrome

Understanding how context (e.g., host species, environmental conditions) drives disease susceptibility is an essential goal of disease ecology. We hypothesized that in bat white-nose syndrome (WNS), species-specific host–pathogen interactions may partly explain varying disease outcomes among host species. We characterized bat and pathogen transcriptomes in paired samples of lesion-positive and lesion-negative wing tissue from bats infected with Pseudogymnoascus destructans in three parallel experiments. The first two experiments analyzed samples collected from the susceptible Nearctic Myotis lucifugus and the less-susceptible Nearctic Eptesicus fuscus, following experimental infection and hibernation in captivity under controlled conditions. The third experiment applied the same analyses to paired samples from infected, free-ranging Myotis myotis, a less susceptible, Palearctic species, following natural infection and hibernation (n = 8 sample pairs/species). Gene expression by P. destructans was similar among the three host species despite varying environmental conditions among the three experiments and was similar within each host species between saprophytic contexts (superficial growth on wings) and pathogenic contexts (growth in lesions on the same wings). In contrast, we observed qualitative variation in host response: M. lucifugus and M. myotis exhibited systemic responses to infection, while E. fuscus up-regulated a remarkably localized response. Our results suggest potential phylogenetic determinants of response to WNS and can inform further studies of context-dependent host–pathogen interactions.解析环境背景（如宿主物种、环境条件）如何影响疾病易感性，是疾病生态学的核心研究目标之一。我们提出假说：在蝙蝠白鼻综合征（white-nose syndrome, WNS）中，宿主与病原体的物种特异性互作，可部分解释不同宿主物种间的疾病转归差异。我们通过三组平行实验，对感染毁灭柱顶囊壳（Pseudogymnoascus destructans）的蝙蝠的病变阳性翼组织与病变阴性翼组织配对样本，开展蝙蝠与病原体的转录组（transcriptomes）表征分析。前两组实验分析了在受控条件下完成人工感染与圈养冬眠后，采集自易感新北界物种小棕蝠（Myotis lucifugus）以及低易感新北界物种大棕蝠（Eptesicus fuscus）的样本。第三组实验则针对经自然感染并冬眠的低易感古北界物种普通鼠耳蝠（Myotis myotis）的野生感染个体的配对样本开展相同分析，每组物种对应8组样本配对（n=8）。尽管三组实验的环境条件存在差异，但毁灭柱顶囊壳（P. destructans）的基因表达模式在三种宿主物种间均保持相似；且在同一宿主物种内，腐生环境（翼表浅层定植）与致病环境（同一翼组织病变处定植）下的基因表达也无显著差异。与之形成鲜明对比的是，宿主的免疫应答存在定性差异：小棕蝠与普通鼠耳蝠均表现出全身性感染应答，而大棕蝠则仅上调了极为局限的局部应答。本研究结果提示了蝙蝠对白鼻综合征应答的潜在系统发育决定因素，可为后续开展背景依赖型宿主-病原体互作研究提供参考。