Orf is a contagious disease caused by the epitheliotropic orf virus (ORFV) that mainly affects goats and sheep. Orf occurs worldwide and can cause great losses to livestock production. Mounting evidence has shown that gut microbiota plays a pivotal role in shaping the immune responses of the host and thus affecting the infection process of a wide range of pathogens. However, it is unclear whether gut microbiota plays a role during orf development. In this study, we exploited asymptomatic ORFV-carrier goats to explore the potential effects of gut microbiota on orf pathogenesis. The results showed that antibiotics-induced gut microbiota disruption significantly aggravated orf, as indicated by the greater disease severity and higher percentage of animals manifesting clinical orf symptoms. Further analysis suggested IL-17-induced excessive neutrophil accumulation in the diseased lips was potentially responsible for the tissue pathology. In addition, skin γδT cells may be an important source of IL-17. In conclusion, our study showed that the gut microbiota of ORFV-carrier goats plays a central role in controlling inflammatory pathology during ORFV infection, partly through suppressing IL-17-mediated local proinflammatory immune responses. This finding can provide help for elucidating the pathogenesis of orf and also suggests an efficient strategy to minimize the inflammatory pathology by maintaining a healthy gut microbiota during orf development.

Orf是一种由上皮性Orf病毒（ORFV）引起的传染性疾病，主要影响山羊和绵羊。Orf遍布全球，可能给牲畜生产造成巨大损失。越来越多的证据表明，肠道菌群在塑造宿主的免疫反应并因此影响多种病原体的感染过程中起着关键作用。然而，尚不清楚肠道菌群是否在orf发育过程中发挥作用。在这项研究中，我们利用无症状ORFV携带山羊来研究肠道菌群对orf发病机理的潜在影响。结果表明，由抗生素引起的肠道微生物群破坏显着加重了orf，这表现为更大的疾病严重度和表现出orf症状的动物百分比更高。进一步的分析表明，IL-17诱导的患病嘴唇中嗜中性粒细胞过度积累可能是造成组织病理的原因。另外，皮肤γδT细胞可能是IL-17的重要来源。总之，我们的研究表明，ORFV携带型山羊的肠道菌群在ORFV感染过程中在控制炎症病理过程中起着核心作用，部分是通过抑制IL-17介导的局部促炎性免疫应答。该发现可以为阐明orf的发病机理提供帮助，并且还提出了通过在orf发育过程中维持健康的肠道菌群来最小化炎性病理的有效策略。我们的研究表明，携带ORFV的山羊的肠道菌群在控制ORFV感染过程中的炎症病理过程中起着核心作用，部分是通过抑制IL-17介导的局部促炎性免疫应答。该发现可以为阐明orf的发病机理提供帮助，并且还提出了通过在orf发育过程中维持健康的肠道菌群来最小化炎性病理的有效策略。我们的研究表明，携带ORFV的山羊的肠道菌群在控制ORFV感染过程中的炎症病理过程中起着核心作用，部分是通过抑制IL-17介导的局部促炎性免疫应答。该发现可以为阐明orf的发病机理提供帮助，并且还提出了通过在orf发育过程中维持健康的肠道菌群来最小化炎性病理的有效策略。