The hijacking of HBV by small extracellular vesicles inhibits M1 macrophages to facilitate immune evasion

• Published in: Scientific reports Vol. 14; no. 1; pp. 19917 - 10
• Main Authors: Zhang, Zili, Liu, Jiamin, Yu, Ling, Zeng, Rong, Pan, Wanlong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/254; 692/420/254; Caspase-1; Extracellular vesicles; Extracellular Vesicles - immunology; Extracellular Vesicles - metabolism; FEN-1; Hep G2 Cells; Hepatitis B - immunology; Hepatitis B - metabolism; Hepatitis B - virology; Hepatitis B virus - immunology; Humanities and Social Sciences; Humans; IL-1β; Immune Evasion; Interleukin 18; Interleukin-18 - metabolism; M1 macrophages; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - virology; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-146a; multidisciplinary; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Science; Science (multidisciplinary); Small extracellular vesicles; THP-1 Cells; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; γ-Interferon; FEN-1; MiR-146a; Immune evasion; Small extracellular vesicles; M1 macrophages
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-70924-3

Small extracellular vesicles (sEVs) have the ability to transfer genetic material between cells, but their role in mediating HBV infection and regulating M1 macrophages to promote immune evasion remains unclear. In this study, we utilized PMA + LPS + IFN-γ to induce THP-1 into M1 macrophages. We then extracted sEVs from HepG2.2.15 cell and treated the M1 macrophages with these sEVs. QPCR detection revealed the presence of HBV-DNA in the M1 macrophages. Additionally, RT-qPCR and WB analysis demonstrated a significantly decreased in the expression of TLR4, NLRP3, pro-caspase-1, caspase-1p20, IL-1β and IL-18 in the M1 macrophages ( P  < 0.05). Furthermore, RT-qPCR results displayed high expression levels of that miR-146a and FEN-1 in the sEVs derived from HepG2.2.15 cells ( P  < 0.01). RT -qPCR and WB analysis showed that these sEVs enhanced the expression of FEN-1 or miR-146a in the M1 macrophages through miR-146a or FEN-1 ( P  < 0.05), while simultaneously reducing the expression of TLR4, NLRP3, caspase-1p20, IL-1β and IL-18 in the M1 macrophages ( P  < 0.05). In summary, our findings indicate that sEVs loaded with HBV inhibit the inflammatory function of M1 macrophages and promote immune escape. Additionally, miR-146a and FEN-1 present in the sEVs play a crucial role in this process.