Immunomodulatory effects of excretory-secretory products, including extracellular vesicles on host immune cell function.

Gastrointestinal nematode infections, particularly , pose challenges to the poultry industry especially in free-range chickens. These nematodes employ sophisticated immunomodulation strategies to evade host immune defences, allowing them to establish chronic infections. Excretory-secretory (ES) products, including extracellular vesicles (EVs), play a pivotal role in host-parasite communication. Thus, this study aimed to investigate the immunomodulatory properties of nematode-derived ES/EVs, and evaluate the impact of ivermectin (IVM) on these interactions . Adult worms were collected from the jejunum of infected chickens and cultured with or without IVM treatment. ES products were collected, and EVs were enriched using size-exclusion chromatography. T-cell proliferation and macrophage activation assays were performed to assess the immunomodulatory effects of ES/EVs. derived ES products suppressed T-cell activation (CD25+CD57+ cells) and reduced blast transformation in both CD4+ and CD8+ T-cells (p<0.05). Furthermore, ES promoted TLR4-induced macrophage NO production, changed macrophage-activated surface phenotype, and inhibited macrophage phagocytosis in high concentration but promoted it in low concentration (p<005). Additionally, derived EVs were detected in culture supernatants, and this EV secretion was decreased with the IVM treatment (p<005). Fourier-transform infrared spectroscopy confirmed IVM treatment altered EV cargo composition. Finally, the EVs influenced cytokine profiles of activated macrophages, decreasing pro-inflammatory cytokine gene expression (IL-1β and IL-8, p<005) which may mirror immune evasion . In summary, this study highlights immunomodulatory mechanisms of ES/EVs and provides fundamental information for developing diagnostic and therapeutic strategies targeting nematode ES products including EVs.Highlights - The ES, including EVs, demonstrate immunomodulatory properties.- ES suppressed T-cell activation, proliferation, and macrophage phagocytosis.- ES including EVs may help in evading host immune system