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

Abstract

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. Adultworms were collected from the jejunum of infected chickens and culturedwith 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 (<&#x2009;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 (<&#x2009;0.05). Additionally,-derived EVs were detected in culture supernatants, and this EV secretion was decreased with the IVM treatment (<&#x2009;0.05). 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-1&#x3b2; and IL-8,<&#x2009;0.05) which may mirror immune evasion. In summary, this study highlights immunomodulatory mechanisms ofES/EVs and provides fundamental information for developing diagnostic and therapeutic strategies targeting nematode ES products including EVs.RESEARCH HIGHLIGHTSExcretory-secretory (ES) products, including extracellular vesicles (EVs), demonstrated immunomodulatory properties.ES suppressed T-cell activation, proliferation, and macrophage phagocytosis.ES, including EVs, may help in evading the host immune system.