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<p>Th17 cells play important roles in anti-infective responses. The 15&#xa0;kDa excretory/secretory protein of <i>Haemonchus contortus</i> (HcES-15) has been identified as a promising immune-protective antigen against <i>H. contortus</i> infection capable of up-regulating IL-17, IL-4 and IL-10 production. To obtain the peptides that primarily induce the Th17 immune response, we amplified and expressed the peptides ES15-1, ES15-2 and ES15-3 from HcES-15. In vitro studies demonstrated that ES15-1 stimulated transcriptional activation of the STAT3/RORγt signaling pathway and induced IL-17 production in goat peripheral blood mononuclear cells (PBMCs). In vivo studies, flow cytometric analysis revealed that subcutaneous injection of PLGA-encapsulated ES15-1 peptide (PLGA-ES15-1, 50&#xa0;μg) significantly enhanced Th17 cell differentiation in the spleens of BALB/c mouse. Consistent with these findings, ELISA quantification demonstrated that ES15-1 treatment significantly increased serum levels of pro-inflammatory cytokine (IL-17, IL-1, IL-6, and TNF-α). In goat immune protection studies, goats (<i>n</i> = 6) were subcutaneously immunized with 500&#xa0;μg of PLGA-ES15-1 on days 0 and 14, followed by infection with <i>H. contortus</i> infective third-stage larvae (iL3s) 1&#xa0;week post-second immunization. ES15-1 significantly enhanced serum levels of pro-inflammatory cytokines (IL-17, IL-1, IL-6, TNF-α). At autopsy, vaccinated goats exhibited 69.0% (<i>p</i> &lt; 0.001) reduction of fecal egg counts (FEC) and 50.54% (<i>p</i> &lt; 0.05) reduction of worm burdens versus controls. Our findings suggested that peptide ES15-1 enhanced Th17 responses through regulation of the STAT3/RORγt pathway, conferring a certain immune protection against <i>H. contortus</i> infection.</p>

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Peptide ES15-1 derived from Haemonchus contortus promotes goat Th17 response by regulating the STAT3/RORγt pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月19日

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  • Cheng Chen,
  • Jiajun Feng,
  • Jilata Amu,
  • Zhaohai Wen,
  • Yangchun Tan,
  • Yongde Xu,
  • Xianglin Pu,
  • Mingmin Lu,
  • Xiaokai Song,
  • Lixin Xu,
  • Xiangrui Li,
  • Ruofeng Yan

摘要

Th17 cells play important roles in anti-infective responses. The 15 kDa excretory/secretory protein of Haemonchus contortus (HcES-15) has been identified as a promising immune-protective antigen against H. contortus infection capable of up-regulating IL-17, IL-4 and IL-10 production. To obtain the peptides that primarily induce the Th17 immune response, we amplified and expressed the peptides ES15-1, ES15-2 and ES15-3 from HcES-15. In vitro studies demonstrated that ES15-1 stimulated transcriptional activation of the STAT3/RORγt signaling pathway and induced IL-17 production in goat peripheral blood mononuclear cells (PBMCs). In vivo studies, flow cytometric analysis revealed that subcutaneous injection of PLGA-encapsulated ES15-1 peptide (PLGA-ES15-1, 50 μg) significantly enhanced Th17 cell differentiation in the spleens of BALB/c mouse. Consistent with these findings, ELISA quantification demonstrated that ES15-1 treatment significantly increased serum levels of pro-inflammatory cytokine (IL-17, IL-1, IL-6, and TNF-α). In goat immune protection studies, goats (n = 6) were subcutaneously immunized with 500 μg of PLGA-ES15-1 on days 0 and 14, followed by infection with H. contortus infective third-stage larvae (iL3s) 1 week post-second immunization. ES15-1 significantly enhanced serum levels of pro-inflammatory cytokines (IL-17, IL-1, IL-6, TNF-α). At autopsy, vaccinated goats exhibited 69.0% (p < 0.001) reduction of fecal egg counts (FEC) and 50.54% (p < 0.05) reduction of worm burdens versus controls. Our findings suggested that peptide ES15-1 enhanced Th17 responses through regulation of the STAT3/RORγt pathway, conferring a certain immune protection against H. contortus infection.