Campfield Brian T, Nolder Christi L, Marinov Anthony, Bushnell Daniel, Davis Amy, Spychala Caressa, Hirsch Raphael, Nowalk Andrew J
Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Department of Pathology, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Microb Pathog. 2014 Aug;73:70-9. doi: 10.1016/j.micpath.2014.04.005. Epub 2014 Apr 24.
Follistatin-like protein 1 (FSTL-1) has recently been described as a critical mediator of CIA and a marker of disease activity. Lyme arthritis, caused by Borrelia burgdorferi, shares similarities with autoimmune arthritis and the experimental murine model collagen-induced arthritis (CIA). Because FSTL-1 is important in CIA and autoimmune arthritides, and Lyme arthritis shares similarities with CIA, we hypothesized that FSTL-1 may be an important mediator of Lyme arthritis. We demonstrate for the first time that FSTL-1 is induced by B. burgdorferi infection and is required for the development of Lyme arthritis in a murine model, utilizing a gene insertion to generate FSTL-1 hypomorphic mice. Using qPCR and qRT-PCR, we found that despite similar early infectious burden, FSTL-1 hypomorphic mice have improved spirochetal clearance in the face of attenuated arthritis and inflammatory cytokine production. Further, FSTL-1 mediates pathogen-specific antibody production and antigen recognition when assessed by ELISA and one- and two-dimensional immunoblotting. This study is the first to describe a role for FSTL-1 in the development of Lyme arthritis and anti-Borrelia response, and the first to demonstrate a role for FSTL-1 in response to infection, highlighting the potential for FSTL-1 as a target in the treatment of B. burgdorferi infection.
卵泡抑素样蛋白1（FSTL-1）最近被描述为胶原诱导性关节炎（CIA）的关键介质和疾病活动的标志物。由伯氏疏螺旋体引起的莱姆关节炎与自身免疫性关节炎以及实验性小鼠模型胶原诱导性关节炎（CIA）有相似之处。由于FSTL-1在CIA和自身免疫性关节炎中很重要，且莱姆关节炎与CIA有相似之处，我们推测FSTL-1可能是莱姆关节炎的重要介质。我们首次证明，利用基因插入产生FSTL-1低表达小鼠，FSTL-1在小鼠模型中由伯氏疏螺旋体感染诱导产生，并且是莱姆关节炎发展所必需的。使用定量聚合酶链反应（qPCR）和定量逆转录聚合酶链反应（qRT-PCR），我们发现尽管早期感染负担相似，但FSTL-1低表达小鼠在关节炎减轻和炎性细胞因子产生减少的情况下，螺旋体清除能力有所提高。此外，通过酶联免疫吸附测定（ELISA）以及一维和二维免疫印迹评估发现，FSTL-1介导病原体特异性抗体产生和抗原识别。本研究首次描述了FSTL-1在莱姆关节炎发展和抗伯氏疏螺旋体反应中的作用，也是首次证明FSTL-1在感染反应中的作用，突出了FSTL-1作为伯氏疏螺旋体感染治疗靶点的潜力。
