Dysbiosis of the gut microbiota maybe exacerbate orf pathology by promoting inflammatory immune responses

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.