Yu Qian, Tang Xiaotian, Hart Thomas, Homer Robert, Belperron Alexia A, Bockenstedt Linda K, Ring Aaron, Nakamura Akira, Fikrig Erol
Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale University, New Haven, United States.
Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.
Elife. 2025 May 20;14:RP104913. doi: 10.7554/eLife.104913.
Lyme disease, caused by , is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected with but only develop mild joint inflammation, was therefore examined. -deficient C57BL/6 mice challenged with had a higher infection load in the tibiotarsal joints and marked periarticular swelling compared to infected wild-type control mice. The ankle joint tissues of infected -deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. -infected -deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT (cterial election to lucidate ost-microbe nteractions in high hroughput) library, we found that SLPI directly interacts with . These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.
莱姆病是美国最常见的蜱传感染疾病,由[病原体名称缺失]引起。关节炎是该感染的主要临床表现,滑膜组织损伤被认为是过度促炎反应所致。分泌型白细胞蛋白酶抑制剂(SLPI)可促进组织修复并发挥抗炎作用。因此,研究了SLPI在C57BL/6小鼠莱姆关节炎发病过程中的作用,C57BL/6小鼠可感染[病原体名称缺失],但仅出现轻度关节炎症。与感染的野生型对照小鼠相比,用[病原体名称缺失]攻击的SLPI基因缺陷型C57BL/6小鼠在胫跗关节处的感染负荷更高,关节周围出现明显肿胀。感染SLPI基因缺陷型小鼠的踝关节组织中浸润的中性粒细胞和巨噬细胞百分比显著更高。感染[病原体名称缺失]的SLPI基因缺陷型小鼠血清中IL-6、中性粒细胞弹性蛋白酶和MMP-8水平也升高。此外,使用最近开发的BASEHIT(用于在高通量下阐明宿主-微生物相互作用的细菌筛选)文库,我们发现SLPI直接与[病原体名称缺失]相互作用。这些数据证明了SLPI在抑制莱姆病关节周围炎症中的重要性。