A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx
antimicrobial peptide
QH301-705.5
Science
Bone Marrow Cells
Microbial Sensitivity Tests
Cell Line
Mice
Immunology and Inflammation
Cathelicidins
cathelicidin
Animals
Humans
Biology (General)
tree frog
Phagocytes
Bacteria
Chemotaxis
Macrophages
Q
R
Fungi
Bacterial Infections
Rats
3. Good health
Mice, Inbred C57BL
Macrophages, Peritoneal
Medicine
amphibian
Female
prophylaxis
phagocyte influx
Anura
DOI:
10.7554/elife.72849
Publication Date:
2022-02-23T09:00:42Z
AUTHORS (10)
ABSTRACT
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 (PopuCATH) from tree frog (Polypedates puerensis) did not 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.
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CITATIONS (21)
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