Peptide Ftt-1 induces Th17-mediated partial protection against Haemonchus contortus in goats

The Th17 immune response is a newly identified response that may play an important role in resistance to Haemonchus contortus (H. contortus) infection. Recombinant protein Hcftt-2 (rHcftt-2) has been shown to impart a degree of immunoprotection in infected goats and is capable of inducing a Th17 immune response. To identify the peptides primarily responsible for inducing the Th17 response, four peptides (Ftt-1, Ftt-2, Ftt-3, and Ftt-4) derived from rHcftt-2 were amplified and expressed. Our studies established that peptide Ftt-1 induces goat PBMCs to secrete IL‑17 in vitro by activating STAT3/RORγt at the transcriptional level. Flow cytometric analysis of splenocytes revealed that subcutaneous immunization of BALB/c mice with PLGA-encapsulated Ftt-1 peptide (50 μg) for 2-3 weeks significantly enhanced splenic Th17 cell populations in vivo. ELISA quantification confirmed that peptide Ftt-1 treatment markedly elevated serum levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17) and Th1-type cytokines (IFN-γ and IL-12) in mice from 1 to 6 weeks post-treatment, while significantly suppressing the typical Th2-type and Treg-type cytokines IL-4 and TGF-β. Furthermore, significant elevation of IL-17, IL-1β, IL-6, TNF-α, IFN-γ, and IL-12 levels, as well as suppression of IL-4 and TGF-β, was observed in goats following two subcutaneous immunizations with PLGA-encapsulated Ftt-1 peptide (500 μg). Necropsy performed five weeks after the oral challenge of goats with 6000 infective third-stage larvae (iL3s) of H. contortus showed a 35.85% reduction in worm burden and a 58.26% reduction in mean fecal egg count (FEC). Our study indicates that Ftt-1 mediates Th17 immune responses, providing partial immune protection against H. contortus infection in goats.