Zhu, Bibo and Wu, Yue and Huang, Su and Zhang, Ruixuan and Son, Young Min and Li, Chaofan and Cheon, In Su and Gao, Xiaochen and Wang, Min and Chen, Yao and Zhou, Xian and Quynh Nguyen, and Phan, Anthony T. and Behl, Supriya and Taketo, M. Mark and Mack, Matthias and Shapiro, Virginia S. and Zeng, Hu and Ebihara, Hideki and Mullon, John J. and Edell, Eric S. and Reisenauer, Janani S. and Demirel, Nadir and Kern, Ryan M. and Chakraborty, Rana and Cui, Weiguo and Kaplan, Mark H. and Zhou, Xiaobo and Goldrath, Ananda W. and Sun, Jie (2021) Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection. IMMUNITY, 54 (6): e9. 1200-+. ISSN 1074-7613, 1097-4180
Full text not available from this repository. (Request a copy)Abstract
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-1 alpha interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1 alpha activities distinguished proliferative and inflammatory AMs in vivo. This beta-catenin-HIF-1 alpha axis was conserved in human AMs and enhanced HIF-1 alpha expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by beta-catenin-HIF-1 alpha signaling, with implications for the treatment of severe respiratory diseases.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLUENZA-VIRUS INFECTION; ALVEOLAR MACROPHAGES; BETA-CATENIN; IMMUNE-RESPONSE; STEM-CELLS; PATHWAY; INTERFERON; PROLIFERATION; HIF-1-ALPHA; ACTIVATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 06:37 |
| Last Modified: | 27 Sep 2022 06:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48005 |
Actions (login required)
 |
View Item |
