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细胞毒性坏死因子 1 通过下调巨噬细胞中 CD36 的转录来诱导急性尿路感染期间的炎症反应。

Cytotoxic Necrotizing Factor 1 Downregulates CD36 Transcription in Macrophages to Induce Inflammation During Acute Urinary Tract Infections.

机构信息

Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, Collaborative Innovation Center for Biotherapy, College of Pharmacy, Nankai University, Tianjin, China.

出版信息

Front Immunol. 2018 Aug 31;9:1987. doi: 10.3389/fimmu.2018.01987. eCollection 2018.

DOI:10.3389/fimmu.2018.01987
PMID:30233583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6128224/
Abstract

Urinary tract infections (UTIs) caused by uropathogenic (UPEC) induce cystitis, pyelonephritis, and can cause kidney scarring and failure if inflammation is not under control. The detailed effects of cytotoxic necrotizing factor 1 (CNF1), the key UPEC toxin, on the pathogenicity of UPEC remain unclear. CD36 is an important scavenger receptor, responsible for pathogen and apoptotic cell clearance, and plays an essential role in host immune defense and homeostasis. Regulation of CD36 by bacterial toxins has not been reported. In this study, using a pyelonephritis mouse model, CNF1 was observed to contribute to increasing neutrophils and bacterial titers in infected bladder and kidney tissues, resulting in severe inflammation and tissue damage. CD36 expression in macrophages was found to be decreased by CNF1 and . We demonstrated that CNF1 attenuated CD36 transcription by decreasing expressions of its upstream transcription factors LXRβ and C/EBPα and their recruitment to the CD36 promotor. In addition, Cdc42 was found to be involved in CNF1-mediated downregulation of LXRβ. Our study investigated the pathogenesis of -carrying UPEC, which affected host innate immune defenses and homeostasis through regulation of CD36 in macrophages during acute UTIs.

摘要

尿路致病性大肠杆菌 (UPEC) 引起的尿路感染会导致膀胱炎、肾盂肾炎,如果炎症得不到控制,还会导致肾脏瘢痕和衰竭。细胞毒性坏死因子 1 (CNF1) 作为 UPEC 的关键毒素,其对 UPEC 致病性的详细影响仍不清楚。CD36 是一种重要的清道夫受体,负责清除病原体和凋亡细胞,在宿主免疫防御和内稳态中发挥重要作用。细菌毒素对 CD36 的调节尚未见报道。在这项研究中,我们使用肾盂肾炎小鼠模型发现,CNF1 有助于增加感染膀胱和肾脏组织中的中性粒细胞和细菌滴度,导致严重的炎症和组织损伤。研究发现 CNF1 下调巨噬细胞中 CD36 的表达。我们证明 CNF1 通过降低其上游转录因子 LXRβ 和 C/EBPα 的表达及其与 CD36 启动子的募集,从而减弱 CD36 的转录。此外,还发现 Cdc42 参与了 CNF1 介导的 LXRβ 下调。我们的研究调查了携带 -的 UPEC 的发病机制,该机制通过在急性尿路感染期间调节巨噬细胞中的 CD36 影响宿主固有免疫防御和内稳态。

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