Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Int Immunopharmacol. 2021 Jul;96:107739. doi: 10.1016/j.intimp.2021.107739. Epub 2021 May 10.
Toll-like receptor 7 (TLR7) is a sensor of microbial ssRNA that participates in the immune response process in many diseases. We herein sought to establish the role of TLR7 in Pseudomonas aeruginosa pneumonia. Pneumonia model was created by intratracheally injecting Pseudomonas aeruginosa and the effects of TLR7 on survival, bacterial burden, lung pathology, cytokine and chemokine production, and pulmonary leukocyte recruitment were measured after Pseudomonas aeruginosa challenge. TLR7 expression was significantly elevated in WT mice after Pseudomonas aeruginosa infection. TLR7 mice demonstrated enhanced survival, bacterial clearance, leukocyte infiltration, and macrophages phagocytic activity, and decreased pathology and capillary leakage. Besides, improved survival and bacterial clearance were observed in WT mice treated with TLR7 antagonist IRS661. More importantly, lack of TLR7 suppressed pro-inflammatory cytokine production and induced anti-inflammatory cytokine production in mice lungs. Finally, neutralized IL-10 damaged the bacterial clearance ability of TLR7 deficient mice, leading to decreased survival. Collectively, absence of TLR7 provided protective effects during Pseudomonas aeruginosa pneumonia and suggested that TLR7 could act as a novel immune target to treat clinical cases with Pseudomonas aeruginosa pneumonia.
Toll 样受体 7（TLR7）是一种微生物 ssRNA 的传感器，参与许多疾病的免疫反应过程。本研究旨在探讨 TLR7 在铜绿假单胞菌肺炎中的作用。通过气管内注射铜绿假单胞菌建立肺炎模型，检测 TLR7 对铜绿假单胞菌感染后小鼠生存、细菌负荷、肺病理、细胞因子和趋化因子产生以及肺白细胞募集的影响。铜绿假单胞菌感染后 WT 小鼠 TLR7 表达明显升高。TLR7 敲除小鼠表现出生存能力增强、细菌清除、白细胞浸润和巨噬细胞吞噬活性增强，以及病理和毛细血管渗漏减少。此外，TLR7 拮抗剂 IRS661 处理的 WT 小鼠也观察到生存能力提高和细菌清除。更重要的是，缺乏 TLR7 抑制了小鼠肺部促炎细胞因子的产生，并诱导抗炎细胞因子的产生。最后，中和 IL-10 削弱了 TLR7 缺陷小鼠的细菌清除能力，导致生存能力下降。总之，TLR7 缺失在铜绿假单胞菌肺炎中提供了保护作用，并表明 TLR7 可作为治疗铜绿假单胞菌肺炎的新型免疫靶点。
