Interleukin 17 Mediates Immunopathology During Orf Development In Goats

Orf as a zoonotic infectious disease,its typical feature is to cause serious pathological tissue damage to the epidermis of the lips.Orf virus colonizes and proliferates in the skin of diseased animals,and replicates in epidermal cells,triggering severe inflammation.Previous studies have found that IL-17 acts on epithelial cells,induces the secretion of various inflammatory cytokines,recruits and activates neutrophils,and promotes their migration to the site of inflammation.Studies have found that IL-17 is highly expressed in similar skin inflammatory diseases,resulting in neutrophil infiltration and even serious pathological tissue damage.Therefore,we speculate that the inflammation of Orf may be related to the inflammatory effect of IL-17.In summary,this experiment links IL-17 with Orf-induced pathological tissue damage,and clarifies the mechanism of immune-pathological tissue damage in goat Orf disease.In this study,PCR and immune-fluorescence staining were used to investigate goat Orf and its pathogenic viruses to determine the diseased goats.Orf diseased goats were used as experimental animals.Inflammatory cell infiltration in the lesion tissue area;it is then linked to the inflammatory cytokines IL-17 and neutrophils,using immunofluorescence staining and real-time PCR technology to study IL-17 and neutrophils,respectively The changes of various related cytokines such as chemokines,explore the role of IL-17 and neutrophils in the inflammatory process and the mechanism of Orf immune-pathological damage.The study achieved the following results: 1.The diseased goat produces typical Orf clinical symptoms and pathological changes.The diseased lips and tissues are positive for PCR detection.Immunofluorescence staining confirms that Orf virus infects goats and accumulates in the skin tissues of goats and lips.The expression level of protein of Orf virus was significantly higher than that of the normal control(P <0.001);2.After Orf virus infected goats,the m RNA expression of neutrophil chemokines CCL4,CXCL6 and IL-8 and granulocyte macrophage colony stimulating factor in lip tissues increased significantly(P <0.05).The number of neutrophils in the tissues and blood increased significantly(P <0.05).The degree of the pathological damage and the degree of inflammation of the lesion tissue were also significantly higher than those of the normal control(P <0.01);3.After Orf virus infected goats,the m RNA expression of IL-17 and its related cytokines IL-23p19,IL-6,IL-1? in lip tissues and peripheral blood mononuclear lymphocytes increased significantly,and the statistical analysis of the results showed that the protein expression of IL-17 at the lesion site was significantly higher than that of the normal control(P <0.001);4.After Orf virus infected goats,immunofluorescence staining found that the expression positions of IL-17 and CD4,IL-17 and ??T almost overlapped,and the statistical analysis of the results found that the lesion site IL-17 and CD4,The expression levels of protein at the overlapping parts of IL-17 and ??T were significantly higher than those of the normal control(P <0.01);5.Orf virus directly stimulates peripheral blood mononuclear lymphocytes,and the m RNA expression levels of IL-17,IL-23p19,IL-6,and IL-1? are significantly increased(P <0.05);6.IL-17 directly stimulated goat lip epithelial cells,and the m RNA expression of neutrophil chemokines IL-8,CXCL6,and CCL4 were significantly increased(P <0.05).Conclusion: 1.The results of Orf lesion tissue found that the invasion of ORFV caused the significant increase of IL-17,IL-17 was recruited to the lesion tissue,and IL-17 mainly mediated the inflammatory response;2.Orf pathological damage results found that a large amount of IL-17 stimulation caused a significant increase in the number of neutrophils,IL-17 recruited a large number of neutrophils to the lesion;3.The results of Orf pathological injury tissues found that a large number of neutrophils were recruited at the lesion site,and the infiltration of neutrophils caused excessive inflammation,which in turn caused severe pathological tissue damage.