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Antimicrobial peptide LL-37 forms complex with bacterial DNA to facilitate blood translocation of bacterial DNA and aggravate ulcerative colitis

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机构: [1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China [2]Life Sciences College of Nanjing Agricultural University, Nanjing 210095, China [3]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China [4]Department of General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China [5]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China [6]Sino-African Joint Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
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关键词: Ulcerative colitis Bacterial DNA LL-37 Immune elimination Chronic inflammation

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Bacterial DNA (bacDNA) is frequently found in serum of patient with ulcerative colitis (UC) and Crohn's disease, even blood bacterial culture is negative. How bacDNA evades immune elimination and is translocated into blood remain unclear. Here, we showed that bacDNA avoids elimination and disables bacteria-killing function of antimicrobial peptide LL-37 (Cramp in mice) by forming complex with LL-37, which is inducible after culture with bacteria or bacterial products. Elevated LL-37-bacDNA complex was found in plasma and lesions of patients with UC. LL-37-bacDNA promoted inflammation by inducing Th1, Th2 and Th17 differentiation and activating toll-like receptor-9 (TLR9). The complex also increased paracellular permeability, which possibly combines its inflammatory effects to promote local damage and bacDNA translocation into blood. Cramp-bacDNA aggravated mouse colitis severity while interference with the complex ameliorated the disease. The study identifies that inflammatogenic bacDNA utilizes LL- 37 as a vehicle for blood translocation and to evade immune elimination. Additionally, bacteria may make a milieu by releasing bacDNA to utilize and resist host antimicrobial peptides as a 'trojan horse'. (C) 2018 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.

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出版当年[2019]版:
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China
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