Immunomodulatory effects of poly(I:C)-stimulated exosomes derived from chicken macrophages
Yeojin Hong1, Jiae Lee1, Thi Hao Vu1
1Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea.
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, thereby inducing the activation of transcription factors such as interferon regulatory factor 3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). 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 I interferons, proinflammatory cytokines, anti-inflammatory cytokines, and chemokines in HD11 and CU91 cells. Moreover, poly(I:C)-stimulated exosomes induced the NF-κB signaling pathway by phosphorylating TAK1 and NF-κB1. Therefore, we suggest that after the activation of Toll-like receptor 3 ligands following infection with dsRNA virus, chicken macrophages regulate the immune response of naive macrophages and T cells through the NF-κB signaling pathway. Furthermore, poly(I:C)-activated exosomes can be potentially utilized as immunostimulators.
Insights
Chicken macrophage exosomes activated by poly(I:C) enhance immune responses in recipient cells. These exosomes stimulate cytokine and chemokine expression, potentially serving as immunostimulators by activating the NF-κB pathway.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Exosomes mediate intercellular communication, carrying proteins and nucleic acids.
- Immune cell-derived exosomes modulate immune responses and recipient cell gene expression.
- Macrophages detect viral dsRNA via Toll-like receptor 3 (TLR3), activating transcription factors like NF-κB.
Purpose of the Study:
- To investigate the immunomodulatory effects of exosomes from chicken macrophages (HD11) stimulated with polyinosinic-polycytidylic acid (poly[I:C]).
- To determine the impact of these exosomes on recipient HD11 cells and CU91 chicken T cells.
Main Methods:
- HD11 chicken macrophage cell line was stimulated with poly(I:C).
- Exosomes were purified from stimulated macrophages.
- Exosomes were delivered into recipient HD11 cells and CU91 chicken T cells.
Main Results:
- Exosomes from poly(I:C)-activated macrophages upregulated type I interferons, pro-inflammatory and anti-inflammatory cytokines, and chemokines in recipient cells.
- These exosomes activated the NF-κB signaling pathway by phosphorylating TAK1 and NF-κB1.
- Poly(I:C)-activated exosomes demonstrate potential as immunostimulators.
Conclusions:
- Chicken macrophage-derived exosomes, upon TLR3 ligand stimulation, regulate immune responses in naive macrophages and T cells via the NF-κB pathway.
- These exosomes represent a promising strategy for immunostimulation in poultry.
- Understanding exosome-mediated communication is crucial for developing novel immunotherapies.
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