PDF(Pubmed)
Abstract：
Digital dermatitis (DD) is a skin disease in cattle characterized by painful inflammatory ulcerative lesions in the feet, mostly associated with local colonization by Treponema spp., including Treponema phagedenis. The reason why most DD lesions remain actively inflamed and progress to chronic conditions despite antibiotic treatment remains unknown. Herein, we show an abundant infiltration of proinflammatory (CD14highCD16low) monocytes/macrophages in active DD lesions, a skin response that was not mitigated by topical treatment with oxytetracycline. The associated bacterium, T. phagedenis, isolated from DD lesions in cattle, when injected subcutaneously into mice, induced abscesses with a local recruitment of Ly6G+ neutrophils and proinflammatory (Ly6ChighCCR2+) monocytes/macrophages, which appeared at infection onset (4 days post challenge) and persisted for at least 7 days post challenge. When exploring the ability of macrophages to regulate inflammation, we showed that bovine blood-derived macrophages challenged with live T. phagedenis or its structural components secreted IL-1β via a mechanism dependent on the NLRP3 inflammasome. This study shows that proinflammatory characteristics of monocytes/macrophages and neutrophils dominate active non-healing ulcerative lesions in active DD, thus likely impeding wound healing after antibiotic treatment.
摘要：
数字皮炎（DD）是牛的一种皮肤病，其特征是脚部疼痛的炎性溃疡性病变，主要与密螺旋体属的局部定植有关。,包括螺旋体。尽管抗生素治疗，大多数DD病变仍然活跃发炎并发展为慢性疾病的原因仍然未知。在这里，我们在活动性DD病变中显示了大量的促炎（CD14highCD16low）单核细胞/巨噬细胞浸润，土霉素局部治疗不能缓解的皮肤反应。相关细菌，T.phagedenis，从牛的DD病变中分离出来，当皮下注射到小鼠体内时，诱导脓肿，局部募集Ly6G+中性粒细胞和促炎（Ly6ChighCCR2+）单核细胞/巨噬细胞，出现在感染发作时（攻击后4天），并在攻击后持续至少7天。当探索巨噬细胞调节炎症的能力时，我们表明，牛血液来源的巨噬细胞受到活的T.phagedenis或其结构成分的攻击，通过依赖于NLRP3炎性体的机制分泌IL-1β。这项研究表明，在活动性DD中，单核细胞/巨噬细胞和中性粒细胞的促炎特征主导着活动性不愈合的溃疡性病变，因此，抗生素治疗后可能会阻碍伤口愈合。
