| First Author | Li Y | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 4 | Pages | 110284 |
| PubMed ID | 35081341 | Mgi Jnum | J:322573 |
| Mgi Id | MGI:6879561 | Doi | 10.1016/j.celrep.2021.110284 |
| Citation | Li Y, et al. (2022) Macrophages activated by hepatitis B virus have distinct metabolic profiles and suppress the virus via IL-1beta to downregulate PPARalpha and FOXO3. Cell Rep 38(4):110284 |
| abstractText | Macrophages display phenotypic plasticity and can be induced by hepatitis B virus (HBV) to undergo either M1-like pro-inflammatory or M2-like anti-inflammatory polarization. Here, we report that M1-like macrophages stimulated by HBV exhibit a strong HBV-suppressive effect, which is diminished in M2-like macrophages. Transcriptomic analysis reveals that HBV induces the expression of interleukin-1beta (IL-1beta) in M1-like macrophages, which display a high oxidative phosphorylation (OXPHOS) activity distinct from that of conventional M1-like macrophages. Further analysis indicates that OXPHOS attenuates the expression of IL-1beta, which suppresses the expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and forkhead box O3 (FOXO3) in hepatocytes to suppress HBV gene expression and replication. Moreover, multiple HBV proteins can induce the expression of IL-1beta in macrophages. Our results thus indicate that macrophages can respond to HBV by producing IL-1beta to suppress HBV replication. However, HBV can also metabolically reprogram macrophages to enhance OXPHOS to minimize this host antiviral response. |
