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A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx

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 p...

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Autores principales: Yang, Yang, Wu, Jing, Li, Qiao, Wang, Jing, Mu, Lixian, Hui, Li, Li, Min, Xu, Wei, Yang, Hailong, Wei, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865851/
https://www.ncbi.nlm.nih.gov/pubmed/35195067
http://dx.doi.org/10.7554/eLife.72849
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author Yang, Yang
Wu, Jing
Li, Qiao
Wang, Jing
Mu, Lixian
Hui, Li
Li, Min
Xu, Wei
Yang, Hailong
Wei, Lin
author_facet Yang, Yang
Wu, Jing
Li, Qiao
Wang, Jing
Mu, Lixian
Hui, Li
Li, Min
Xu, Wei
Yang, Hailong
Wei, Lin
author_sort Yang, Yang
collection PubMed
description 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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spelling pubmed-88658512022-02-24 A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx Yang, Yang Wu, Jing Li, Qiao Wang, Jing Mu, Lixian Hui, Li Li, Min Xu, Wei Yang, Hailong Wei, Lin eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2022-02-23 /pmc/articles/PMC8865851/ /pubmed/35195067 http://dx.doi.org/10.7554/eLife.72849 Text en © 2022, Yang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Yang, Yang
Wu, Jing
Li, Qiao
Wang, Jing
Mu, Lixian
Hui, Li
Li, Min
Xu, Wei
Yang, Hailong
Wei, Lin
A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx
title A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx
title_full A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx
title_fullStr A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx
title_full_unstemmed A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx
title_short A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx
title_sort non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865851/
https://www.ncbi.nlm.nih.gov/pubmed/35195067
http://dx.doi.org/10.7554/eLife.72849
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