Natural resistance to worms exacerbates bovine tuberculosis severity independently of worm coinfection.
Natural resistance to worms exacerbates bovine tuberculosis severity independently of worm coinfection.
复制标题
对蠕虫的天然抵抗力会加剧牛结核病的严重程度，与蠕虫合并感染无关。
DOI：
10.1073/pnas.2015080118
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发表时间：
2021
影响因子：
11.1
通讯作者：
Sakamoto,Kaori
中科院分区：
文献类型：
--
作者：
Ezenwa,VanessaO;Budischak,SarahA;Buss,Peter;Seguel,Mauricio;Luikart,Gordon;Jolles,AnnaE;Sakamoto,Kaori
在合并感染期间产生的病原体相互作用可加剧疾病的严重程度，例如当针对一种病原体的免疫应答对另一种病原体的防御产生负面影响时。宿主对病原体的免疫反应，由宿主和病原体之间的历史进化相互作用形成，也可能以对其他病原体产生影响的方式改变宿主的免疫防御。在这种情况下，即使没有并发感染，两种病原体之间的负面相互作用也可能出现。寄生虫和结核病（TB）涉及地理上最广泛的病原体相互作用之一，在合并感染期间，蠕虫可加重TB疾病的后果。在这里，我们表明，在野生哺乳动物的自然抵抗蠕虫影响牛结核病（BTB）的严重程度独立的活动蠕虫感染。我们发现，抗虫个体比非抗虫个体更容易死于BTB，并且他们的疾病进展更快。驱虫治疗缓和，但没有消除，电阻的效果，电阻和治疗的效果是相反的和加性的，未经处理的，电阻的个人经历最高的死亡率。此外，抗性和驱虫治疗对BTB病理学的影响不重叠。耐药性的影响表现在肺（BTB感染的主要部位），而治疗的影响几乎完全表现在淋巴结（播散性疾病的部位），这表明耐药性和活跃的蠕虫感染通过不同的机制影响BTB的进展。我们的研究结果表明，病原体之间的相互作用可能是在非常不同的时间尺度上发生的过程的结果。
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.