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

Zilei Duan; Yaqun Fang; Yang Sun; Ning Luan; Xue Chen; Mengrou Chen; Yajun Han; Yizhu Yin; James Mwangi; Junkun Niu; Kunhua Wang; Yinglei Miao; Zhiye Zhang; Ren Lai

doi:10.1016/j.scib.2018.09.014

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

Sci Bull (Beijing). 2018 Oct 30;63(20):1364-1375. doi: 10.1016/j.scib.2018.09.014. Epub 2018 Sep 22.

Authors

Zilei Duan¹, Yaqun Fang², Yang Sun³, Ning Luan², Xue Chen⁴, Mengrou Chen², Yajun Han¹, Yizhu Yin⁴, James Mwangi⁵, Junkun Niu³, Kunhua Wang⁶, Yinglei Miao⁷, Zhiye Zhang⁸, Ren Lai⁹

Affiliations

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 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China.
⁵ 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China; Sino-African Joint Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
⁶ Department of General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
⁷ Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China. Electronic address: [email protected].
⁸ 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. Electronic address: [email protected].
⁹ 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; Sino-African Joint Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Electronic address: [email protected].

PMID: 36658908
DOI: 10.1016/j.scib.2018.09.014

Abstract

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'.

Keywords: Bacterial DNA; Chronic inflammation; Immune elimination; LL-37; Ulcerative colitis.