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’.

溃疡性结肠炎（UC）和克罗恩病患者的血清中经常发现细菌DNA（bacDNA），甚至血细菌培养也是阴性的。bacDNA 如何逃避免疫消除并转移到血液中仍不清楚。在这里，我们表明 bacDNA 通过与 LL-37 形成复合物来避免消除和禁用抗菌肽 LL-37（小鼠抽筋）的杀菌功能，后者在与细菌或细菌产物培养后可被诱导。在 UC 患者的血浆和病变中发现升高的 LL-37-bacDNA 复合物。LL-37-bacDNA 通过诱导 Th1、Th2 和 Th17 分化并激活 toll 样受体 9 (TLR9​​) 来促进炎症。该复合物还增加了细胞旁通透性，这可能结合其炎症作用促进局部损伤和 bacDNA 易位到血液中。Cramp-bacDNA 加重了小鼠结肠炎的严重程度，而干扰该复合物则改善了疾病。该研究确定致炎性 bacDNA 利用 LL-37 作为血液转运和逃避免疫消除的载体。此外，细菌可以通过释放 bacDNA 来利用和抵抗宿主抗菌肽作为“特洛伊木马”来创造环境。