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

Authors: HONG, YEOJIN - Chung-Ang University; LEE, JIAE - Chung-Ang University; VU, THI HAO - Chung-Ang University; LEE, SOOYEON - Chung-Ang University; Lillehoj, Hyun; HONG, YEONG HO - Chung-Ang University

Submitted to: Developmental and Comparative Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2020
Publication Date: 10/22/2020
Citation: Hong, Y., Lee, J., Vu, T., Lee, S., Lillehoj, H.S., Hong, Y. 2020. Exosomes of lipopolysaccharide-stimulated chicken macrophages modulate immune response through the MyD88/NF-kB signaling pathway. Developmental and Comparative Immunology. https://doi.org/10.1016/j.dci.2020.103908.
DOI: https://doi.org/10.1016/j.dci.2020.103908

Interpretive Summary: Understanding how host immune response in poultry is regulated following an initial immune recognition by macrophages is important to develop a vaccination strategy. In this paper, ARS scientists collaborated with scientists at the Chung Ang University in South Korea to study how the small membrane vesicles called “Exosomes” which are present in most biological fluids activate innate immunity. These exosomes are produced from multivesicular bodies and play a role in cell-to-cell signaling by releasing their contents. The purpose of this study was to demonstrate the immunoregulatory functions of these exosomes in innate immune response in chickens. The results showed that chicken macrophages cells which were activated with lipopolysaccharides (LPS) which are large membrane molecules of bacteria, released exosomes that affected host immunity by stimulating the production of cytokines and chemokines through a special molecular signaling pathway. This is the first finding in chickens to show that the exosomes from bacteria-stimulated chicken macrophage cells modulated the pathways associated with host innate immune response. These results clearly show the important function of exosomes in regulating early immune response and their potential application as novel immune modulator to enhance early phase of host immunity in chickens.

Technical 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, macrophage recognizes lipopolysaccharide (LPS) of Gram-negative bacteria by toll-like receptors 4 (TLR4) and intracellular pathway such as NF-'B is activated inducing proinflammatory cytokines expression. 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-1ß, IFN-', IFN-a, IL-4, CCL4, CCL17, and CCL19, in naive chicken macrophage cells. Furthermore, LPS-activated exosomes induced the MyD88/NF-'B 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-'B signaling pathway.