A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx.
Yang Yang, Jing Wu, Qiao Li, Jing Wang, Lixian Mu, Li Hui, Min Li, Wei Xu, Hailong Yang, Lin Wei
Author Information
Yang Yang: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
Jing Wu: School of Basic Medical Sciences, Kunming Medical University, Kunming, China.
Qiao Li: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
Jing Wang: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
Lixian Mu: School of Basic Medical Sciences, Kunming Medical University, Kunming, China.
Li Hui: The Affiliated Guangji Hospital of Soochow University, Suzhou, China.
Min Li: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
Wei Xu: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
Hailong Yang: School of Basic Medical Sciences, Kunming Medical University, Kunming, China.
Lin Wei: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. ORCID
The roles of bactericidal cathelicidins against bacterial infection have been extensively studied. However, the antibacterial property and mechanism of action of non-bactericidal cathelicidins are rarely known. Herein, a novel naturally occurring cathelicidin (CATH) from tree frog () did not't show any direct anti-bacterial activity in vitro. Intriguingly, intraperitoneal injection of CATH before bacterial inoculation significantly reduced the bacterial load in tree frogs and mice, and reduced the inflammatory response induced by bacterial inoculation in mice. CATH 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 CATH significantly drove the leukocyte influx in both frogs and mice. In mice, CATH 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 CATH. CATH did not directly act as chemoattractant for phagocytes, but CATH obviously drove phagocyte migration when it was cultured with macrophages. CATH significantly elicited chemokine/cytokine production in macrophages through activating p38/ERK mitogen-activated protein kinases (MAPKs) and NF-κB p65. CATH markedly enhanced neutrophil phagocytosis via promoting the release of neutrophil extracellular traps (NETs). Additionally, CATH showed low side effects both in vitro and in vivo. Collectively, CATH 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 CATH to prevent bacterial infection.
