Chicken cathelicidin-3 protected mice from avian pathogenic Escherichia coli infection mediated by triggering chemokine CCL3 pathway
Abstract
Host defense peptides (HDPs) possess both direct bacteriocidal and immunomodulatory activities. In this study, chicken cathelicidin-1 (cCATH-1) and chicken cathelicidin-3 (cCATH-3) were selected based on their markedly different minimum inhibitory concentrations (MICs) against avian pathogenic Escherichia coli (APEC) strains, with MICs of cCATH-1 being 4- to 16-fold lower than those of cCATH-3. However, following intraperitoneal challenge with APEC strain E058 (4 × 10⁶ CFU/mouse), 80% of cCATH-3 treated mice survived while 20% of cCATH-1 treated mice survived. Flow cytometry (FC) revealed significantly lower peripheral blood Ly6Chigh monocytes but higher peritoneal Ly6Chigh macrophages in cCATH-3-treated mice at 4 and 8 h post-treatment. Peritoneal CCL3 secretion was significantly upregulated in cCATH-3 treated mice at 8 h post-treatment. Upon knockout of macrophages, the protection of cCATH-3 in mice against APEC E058 challenge was markedly abolished. In vitro, peritoneal macrophages treated with cCATH-3 showed stronger bacteriocidal activity than those treated with cCATH-1. Mouse CCL-3 (mCCL3)-specific antibody neutralize the effect of mCCL3 on macrophages chemotaxis in vitro. mCCL3-specific antibody administration resulted in 0% survival in cCATH-3-treated mice versus 60% survival in cCATH-3-treated mice administered with mock antibody, while cCATH-1-treated mice showed 0% survival administered with either mCCL3-specific antibody or mock antibody after APEC E058 strain challenge. In summary, cCATH-3 provides robust protection against APEC infection compared with cCATH-1 in mice, partially through CCL3-mediated macrophage chemotaxis and enhanced bacteriocidal activity in activated macrophages, revealing a novel mechanism of avian cathelicidins and supporting HDPs as alternatives to antibiotics for controlling avian colibacillosis.
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BibTeX
@article{jiang2026chicken,
title = {{Chicken cathelicidin-3 protected mice from avian pathogenic Escherichia coli infection mediated by triggering chemokine CCL3 pathway}},
author = {Luyao Jiang and Fan Yang and Jiayan Wu and Zhengliang Li and Xiemin Zhu and Hao Pan and Shaotong Zhang and Haochun Pan and Hang Wang and Jingting Yao and Ping Yan and Qingqing Gao and Changchao Huan and Song Gao and Xinan Jiao and Xiufan Liu},
journal = {Veterinary Research},
year = {2026},
month = oct,
doi = {10.1186/s13567-026-01844-5},
url = {https://hal.science/hal-05793440v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Chicken cathelicidin-3 protected mice from avian pathogenic Escherichia coli infection mediated by triggering chemokine CCL3 pathway
AU - Luyao Jiang
AU - Fan Yang
AU - Jiayan Wu
AU - Zhengliang Li
AU - Xiemin Zhu
AU - Hao Pan
AU - Shaotong Zhang
AU - Haochun Pan
AU - Hang Wang
AU - Jingting Yao
AU - Ping Yan
AU - Qingqing Gao
AU - Changchao Huan
AU - Song Gao
AU - Xinan Jiao
AU - Xiufan Liu
PY - 2026
DA - 2026/10/12
JO - Veterinary Research
DO - 10.1186/s13567-026-01844-5
UR - https://hal.science/hal-05793440v1
AB - Host defense peptides (HDPs) possess both direct bacteriocidal and immunomodulatory activities. In this study, chicken cathelicidin-1 (cCATH-1) and chicken cathelicidin-3 (cCATH-3) were selected based on their markedly different minimum inhibitory concentrations (MICs) against avian pathogenic Escherichia coli (APEC) strains, with MICs of cCATH-1 being 4- to 16-fold lower than those of cCATH-3. However, following intraperitoneal challenge with APEC strain E058 (4 × 10⁶ CFU/mouse), 80% of cCATH-3 treated mice survived while 20% of cCATH-1 treated mice survived. Flow cytometry (FC) revealed significantly lower peripheral blood Ly6Chigh monocytes but higher peritoneal Ly6Chigh macrophages in cCATH-3-treated mice at 4 and 8 h post-treatment. Peritoneal CCL3 secretion was significantly upregulated in cCATH-3 treated mice at 8 h post-treatment. Upon knockout of macrophages, the protection of cCATH-3 in mice against APEC E058 challenge was markedly abolished. In vitro, peritoneal macrophages treated with cCATH-3 showed stronger bacteriocidal activity than those treated with cCATH-1. Mouse CCL-3 (mCCL3)-specific antibody neutralize the effect of mCCL3 on macrophages chemotaxis in vitro. mCCL3-specific antibody administration resulted in 0% survival in cCATH-3-treated mice versus 60% survival in cCATH-3-treated mice administered with mock antibody, while cCATH-1-treated mice showed 0% survival administered with either mCCL3-specific antibody or mock antibody after APEC E058 strain challenge. In summary, cCATH-3 provides robust protection against APEC infection compared with cCATH-1 in mice, partially through CCL3-mediated macrophage chemotaxis and enhanced bacteriocidal activity in activated macrophages, revealing a novel mechanism of avian cathelicidins and supporting HDPs as alternatives to antibiotics for controlling avian colibacillosis.
SN - 0928-4249
SN - 1297-9716
ER -