The roles of bactericidal cathelicidins against bacterial infection have been extensively studied. However, the anti-bacterial property and mechanism of action of non-bactericidal cathelicidins are rarely known. Herein, a novel naturally occurring cathelicidin (PopuCATH) from tree frog (Polypedates puerensis) didn’t show any direct anti-bacterial activity in vitro. Intriguingly, intraperitoneal injection of PopuCATH before bacterial inoculation significantly reduced the bacterial load in tree frogs and mice, and reduced the inflammatory response induced by bacterial inoculation in mice. PopuCATH pretreatment also increased the survival rates of septic mice induced by a lethal dose of bacterial inoculation or cecal ligation and puncture (CLP). Intraperitoneal injection of PopuCATH significantly drove the leukocyte influx in both frogs and mice. In mice, PopuCATH rapidly drove neutrophil, monocyte/macrophage influx in mouse abdominal cavity and peripheral blood with a negligible impact on T and B lymphocytes, and neutrophils, monocytes/macrophages, but not T and B lymphocytes, were required for the preventive efficacy of PopuCATH. PopuCATH did not directly act as chemoattractant for phagocytes, but PopuCATH obviously drove phagocyte migration when it was cultured with macrophages. PopuCATH significantly elicited chemokine/cytokine production in macrophages through activating p38/ERK mitogen-activated protein kinases (MAPKs) and NF-κB p65. PopuCATH markedly enhanced neutrophil phagocytosis via promoting the release of neutrophil extracellular traps (NETs). Additionally, PopuCATH showed low side effects both in vitro and in vivo. Collectively, PopuCATH acts as a host-based immune defense regulator that provides prophylactic efficacy against bacterial infection without direct antimicrobial effects. Our findings reveal a non-bactericidal cathelicidin which possesses unique anti-bacterial action, and highlight the potential of PopuCATH to prevent bacterial infection.

中文翻译：

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一种非杀菌性导管素通过驱动吞噬细胞流入提供预防细菌感染的功效

已经广泛研究了杀菌导管素对细菌感染的作用。然而，非杀菌性导管素的抗菌特性和作用机制鲜为人知。在此，来自树蛙（Polypedates puerensis）的一种新型天然导管素（Popu CATH）在体外没有表现出任何直接的抗菌活性。有趣的是，细菌接种前腹腔注射Popu CATH 显着降低了树蛙和小鼠的细菌负荷，并减少了小鼠细菌接种引起的炎症反应。波普CATH 预处理还增加了致死剂量的细菌接种或盲肠结扎和穿刺 (CLP) 诱导的败血症小鼠的存活率。Popu CATH 的腹腔注射显着推动了青蛙和小鼠的白细胞流入。在小鼠中，Popu CATH 迅速驱使小鼠腹腔和外周血中的中性粒细胞、单核细胞/巨噬细胞流入，对 T 和 B 淋巴细胞的影响可以忽略不计，并且需要中性粒细胞、单核细胞/巨噬细胞，而不是 T 和 B 淋巴细胞，以达到预防效果的珀普CATH。Popu CATH不直接作为吞噬细胞的化学引诱物，但Popu CATH与巨噬细胞一起培养时明显促进了吞噬细胞的迁移。Popu CATH 通过激活 p38/ERK 丝裂原活化蛋白激酶 (MAPK) 和 NF-κB p65，显着引发巨噬细胞中趋化因子/细胞因子的产生。Popu CATH 通过促进中性粒细胞胞外陷阱 (NETs) 的释放显着增强中性粒细胞吞噬作用。此外，Popu CATH在体外和体内均显示出低副作用。总的来说，Popu CATH 作为一种基于宿主的免疫防御调节剂，可提供针对细菌感染的预防功效，而没有直接的抗菌作用。我们的研究结果揭示了一种具有独特抗菌作用的非杀菌性导管素，并突出了Popu的潜力CATH防止细菌感染。