A Trifecta of New Insights into Ovine Footrot for Infection Drivers, Immune Response, and Host-Pathogen Interactions.
A Trifecta of New Insights into Ovine Footrot for Infection Drivers, Immune Response, and Host-Pathogen Interactions.
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DOI：
10.1128/iai.00270-21
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发表时间：
2021-09-16
影响因子：
3.1
通讯作者：
Tötemeyer S
中科院分区：
文献类型：
--
作者：
Blanchard AM;Staley CE;Shaw L;Wattegedera SR;Baumbach CM;Michler JK;Rutland C;Back C;Newbold N;Entrican G;Tötemeyer S
蹄疾是一种多微生物传染病，会导致绵羊严重跛行，导致该行业最大的福利问题之一。FOOSTRATE的复杂病因使得在原位或体外研究变得困难。计算方法为了解所涉及的细菌以及它们可能如何与宿主相互作用提供了一种解决方案，最终为未来以假设为导向的研究工作提供了一种识别目标的方法。在这里，我们首次使用后转录组学对健康和患病的绵羊足部在自然多菌感染状态下的细菌群落转录本与宿主免疫反应进行了联合的全球分析。分析了皮肤内部和表面的细菌种群以及最丰富的细菌转录本，表明脚步影响的皮肤不仅减少了引起结节双歧杆菌的多样性，增加了其丰度，而且还减少了其他物种的多样性，如发酵支原体和解糖卟啉单胞菌。宿主转录学揭示了与皮肤屏障功能、血管功能和免疫监视相关的生物学过程在不健康的指间皮肤中受到抑制，组织学研究发现，与外表健康的皮肤相比，受脚步影响的指间皮肤中I型胶原(与疤痕组织形成相关)显著增加。最后，我们提供了一些与毒力基因和宿主剪接体相关的宿主和病原体相互作用的有趣迹象，这可能导致识别未来的治疗靶点。
Footrot is a polymicrobial infectious disease in sheep causing severe lameness, leading to one of the industry’s largest welfare problems. The complex etiology of footrot makes in situ or in vitro investigations difficult. Computational methods offer a solution to understanding the bacteria involved and how they may interact with the host, ultimately providing a way to identify targets for future hypothesis-driven investigative work. Here, we present the first combined global analysis of bacterial community transcripts together with the host immune response in healthy and diseased ovine feet during a natural polymicrobial infection state using metatranscriptomics. The intratissue and surface bacterial populations and the most abundant bacterial transcriptomes were analyzed, demonstrating that footrot-affected skin has reduced diversity and increased abundances of not only the causative bacterium Dichelobacter nodosus but also other species such as Mycoplasma fermentans and Porphyromonas asaccharolytica. Host transcriptomics reveals the suppression of biological processes related to skin barrier function, vascular functions, and immunosurveillance in unhealthy interdigital skin, supported by histological findings that type I collagen (associated with scar tissue formation) is significantly increased in footrot-affected interdigital skin compared to outwardly healthy skin. Finally, we provide some interesting indications of host and pathogen interactions associated with virulence genes and the host spliceosome, which could lead to the identification of future therapeutic targets.