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

TL;DR

A peptide from a parasitic worm boosts Th17 immune responses in goats by activating a specific signaling pathway, offering protection against infection.

Contribution

The study identifies a specific peptide (ES15-1) that enhances Th17 responses via the STAT3/RORγt pathway in goats.

Findings

ES15-1 activates the STAT3/RORγt pathway and increases IL-17 production in goat PBMCs.

PLGA-encapsulated ES15-1 significantly enhances Th17 cell differentiation in mice and reduces worm burdens in goats.

ES15-1 treatment increases pro-inflammatory cytokine levels and reduces fecal egg counts in goats.

Abstract

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.

Figures