Natural resistance to worms exacerbates bovine tuberculosis severity independently of worm coinfection
Natural resistance to worms exacerbates bovine tuberculosis severity independently of worm coinfection
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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：
10.1101/2020.08.26.262683
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
K. Sakamoto
中科院分区：
文献类型：
--
作者：
V. Ezenwa;S. Budischak;P. Buss;M. Seguel;G. Luikart;A. Jolles;K. Sakamoto
重要的是，病原体之间的相互作用可能会对宿主健康产生实质性的负面影响。因此，确定这些相互作用的原因对于有效的疾病管理和控制是不可或缺的。同时或顺序感染同一宿主的两种病原体之间的相互作用是常见的。我们表明，当对一种病原体的遗传防御影响对另一种病原体的反应时，也会发生相互作用，即使第一种病原体同时缺失。病原体相互作用的这种模式为理解自然人群中疾病严重程度的变异模式提供了洞察力。这也意味着，在某些情况下，依赖于选择对一种病原体的抗性的控制策略，例如在牲畜中，可能会危及对另一种病原体的控制。在合并感染过程中出现的病原体相互作用可能会加剧疾病的严重性，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。宿主对病原体的免疫反应也可能是由宿主和病原体之间的历史进化相互作用形成的，可能会改变宿主的免疫防御，从而对其他病原体产生影响。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相互作用。寄生虫和结核病(TB)参与了病原体在地理上最广泛的相互作用之一，在合并感染期间，蠕虫可能会加剧结核病的疾病结局。在这里，我们展示了在野生哺乳动物中，对蠕虫的自然抵抗力独立于活跃的蠕虫感染影响牛结核病(BTB)的严重程度。我们发现，抗虫个体比不抗虫个体更有可能死于BTB，而且他们的疾病进展更快。驱虫剂处理减缓了抗性效应，但没有消除，抗性和处理的影响是相反的和相加的，未处理的抗性个体经历了最高的死亡率。此外，抗药性和驱虫药治疗对BTB的病理影响不重叠。耐药性的影响表现在肺部(BTB的主要感染部位)，而治疗的效果几乎完全表现在淋巴结(播散性疾病的部位)，这表明耐药性和活动性蠕虫感染通过不同的机制影响BTB的进展。我们的发现表明，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。
Significance Interactions between pathogens can have substantial negative effects on host health. Therefore, identifying the causes of these interactions is integral for effective disease management and control. Interactions between two pathogens that simultaneously or sequentially infect the same host are common. We show that interactions also arise when genetically based defenses against one pathogen affect responses to another, even when the first pathogen is concurrently absent. This mode of pathogen interaction provides insight for understanding patterns of variation in disease severity in natural populations. It also implies that, under some conditions, control strategies that rely on selecting for resistance to one pathogen, in livestock for example, might jeopardize control of another. 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.
影响因子：
16.8
作者：
Babu S;Nutman TB
通讯作者：
Nutman TB
影响因子：
15.9
作者：
Monin, Leticia;Griffiths, Kristin L.;Khader, Shabaana A.
通讯作者：
Khader, Shabaana A.