Pathogen interactions arising during coinfection can exacerbate disease severity, for example when the immune response mounted against one pathogen negatively affects defense of another. It is also possible that host immune responses to a pathogen, shaped by historical evolutionary interactions between host and pathogen, may modify host immune defenses in ways that have repercussions for other pathogens. In this case, negative interactions between two pathogens could emerge even in the absence of concurrent infection. Parasitic worms and tuberculosis (TB) are involved in one of the most geographically extensive of pathogen interactions, and during coinfection worms can exacerbate TB disease outcomes. Here, we show that in a wild mammal natural resistance to worms affects bovine tuberculosis (BTB) severity independently of active worm infection. We found that worm-resistant individuals were more likely to die of BTB than were nonresistant individuals, and their disease progressed more quickly. Anthelmintic treatment moderated, but did not eliminate, the resistance effect, and the effects of resistance and treatment were opposite and additive, with untreated, resistant individuals experiencing the highest mortality. Furthermore, resistance and anthelmintic treatment had nonoverlapping effects on BTB pathology. The effects of resistance manifested in the lungs (the primary site of BTB infection), while the effects of treatment manifested almost entirely in the lymph nodes (the site of disseminated disease), suggesting that resistance and active worm infection affect BTB progression via distinct mechanisms. Our findings reveal that interactions between pathogens can occur as a consequence of processes arising on very different timescales.

共感染期间出现的病原体相互作用会加剧疾病的严重程度，例如当针对一种病原体的免疫反应对另一种病原体的防御产生负面影响时。由宿主和病原体之间的历史进化相互作用形成的宿主对病原体的免疫反应也可能以对其他病原体产生影响的方式改变宿主免疫防御。在这种情况下，即使在没有并发感染的情况下，两种病原体之间也可能出现负面相互作用。寄生虫和结核病 (TB) 参与了地理上最广泛的病原体相互作用之一，在共感染期间，蠕虫会加剧结核病的后果。在这里，我们表明，在野生哺乳动物中，对蠕虫的自然抗性会影响牛结核病 (BTB) 的严重程度，而与活跃的蠕虫感染无关。我们发现抗虫个体比非抗虫个体更有可能死于 BTB，并且他们的疾病进展更快。驱虫治疗缓和但没有消除抗性效应，抗性和治疗的影响是相反的和相加的，未经治疗的抗性个体的死亡率最高。此外，抗性和驱虫治疗对 BTB 病理学具有非重叠效应。耐药性的影响表现在肺部（BTB 感染的主要部位），而治疗的效果几乎完全表现在淋巴结（传播性疾病的部位），这表明耐药性和活动性蠕虫感染通过不同的机制影响 BTB 进展.