Exosomes of lipopolysaccharide-stimulated chicken macrophages modulate immune response through the MyD88/NF-κB signaling pathway

Abstract

Exosomes are small membrane-extracellular vesicles produced from multivesicular bodies and play a role in cell-to-cell signaling. Exosomes from immune cells can regulate immune responses of recipient cells by releasing their contents. In the immune system, macrophages recognize lipopolysaccharides (LPSs) of gram-negative bacteria by toll-like receptor 4 (TLR4) and intracellular pathways, such as NF-κB pathway, are activated, inducing proinflammatory cytokine expression. However, no studies have investigated the functions of exosomes in chicken macrophages. The purpose of this study was to demonstrate the immunoregulatory functions of LPS-activated exosomes in chicken immune systems. Therefore, chicken macrophages cells (HD11) were activated with LPS, and exosomes were purified. The LPS-activated exosomes enhanced the gene expression of cytokines and chemokines, including IL-1β, IFN-γ, IFN-α, IL-4, CCL4, CCL17, and CCL19, in naive chicken macrophages. Furthermore, LPS-activated exosomes induced the MyD88/NF-κB signaling pathway. Therefore, as an immune response against gram-negative bacterial infection, LPS-activated chicken macrophages can release exosomes that are delivered to inactivated macrophages by regulating the expression of immune-related genes and the MyD88/NF-κB signaling pathway. In the future, LPS-stimulated exosomes may be utilized as an immune stimulator.

Keywords: Chicken; Exosomes; Lipopolysaccharide; Macrophage; NF-κB signaling pathway.