| First Author | Zhu B | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 6 | Pages | 1200-1218.e9 |
| PubMed ID | 33951416 | Mgi Jnum | J:306906 |
| Mgi Id | MGI:6706739 | Doi | 10.1016/j.immuni.2021.04.001 |
| Citation | Zhu B, et al. (2021) Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection. Immunity |
| abstractText | Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/beta-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs) . Activation of beta-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, beta-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted beta-catenin-HIF-1alpha interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1alpha activities distinguished proliferative and inflammatory AMs in vivo. This beta-catenin-HIF-1alpha axis was conserved in human AMs and enhanced HIF-1alpha expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by beta-catenin-HIF-1alpha signaling, with implications for the treatment of severe respiratory diseases. |
