Immunomodulatory effects of poly (I:C)-stimulated exosomes derived from chicken macrophages

Authors: HONG, YEOJIN - Chung-Ang University; LEE, JIAE - Chung-Ang University; VU, THI - Chung-Ang University; Lillehoj, Hyun; HONG, YEON - Chung-Ang University

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2021
Publication Date: 8/1/2021
Citation: Hong, Y., Lee, J., Vu, T.H., Lillehoj, H.S., Hong, Y.H. 2021. Immunomodulatory effects of poly (I:C)-stimulated exosomes derived from chicken macrophages. International Journal of Molecular Sciences. https://doi.org/10.1016/j.psj.2021.101247.
DOI: https://doi.org/10.1016/j.psj.2021.101247

Interpretive Summary: Understanding how animal immune cells communicate with each other to initiate immune response against many pathogens is critical for vaccine development. The process of how immune cells, especially macrophage which are known to present antigens to host lymphocytes to initiate immune response to infectious agents, needs to be better understood for development of preventive measures against pathogens. Exosomes are small membrane vesicles that contain proteins and nucleic acids derived from macrophages and are known to mediate intracellular communication In this paper, scientists at a Korean university collaborated with ARS scientists in Beltsville to demonstrate how small membrane bound exosomes communicate with critical receptors of host immune cells to trigger immune response to antigens. This study showed in detail what kind of immune mediators are stimulated by the exosomes derived from chicken macrophages upon stimulation by poly(I:C). Upon stimulation, many key immunomodulating molecules called cytokines and chemokines were produced. These results enhance our understanding of the mechanisms underlying the action of exosomes in chicken immune response and will facilitate developing effective strategy to vaccinate animals against infectious disease.

Technical Abstract: Exosomes are small membrane vesicles that contain proteins and nucleic acids derived from secretory cells and mediate intracellular communication. Immune cell-derived exosomes regulate immune responses and gene expression of recipient cells. Macrophages recognize viral dsRNA via Toll-like receptor 3 (TLR3), thereby inducing the activation of transcription factors such as interferon regulatory factor 3 (IRF3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-'B). In this study, we aimed to identify the immunomodulatory functions of exosomes derived from chicken macrophages (HD11) stimulated with polyinosinic-polycytidylic acid (poly[I:C]); exosomes were then delivered into HD11 cells and CU91 chicken T cells. Exosomes purified from poly(I:C)-activated macrophages stimulated the expression of type 1 interferons, pro-inflammatory cytokines, anti-inflammatory cytokines, and chemokines in HD11 and CU91 cells. Moreover, poly(I:C)-stimulated exosomes induced the NF-'B signaling pathway by phosphorylating TAK1 and NF-'B1. Therefore, we suggest that after the activation of TLR3 ligands following infection with dsRNA virus, chicken macrophages regulate the immune response of naive macrophages and T cells through the NF-'B signaling pathway. Furthermore, poly(I:C)-activated exosomes can be potentially utilized as immunostimulators.