Academic Journal
Trained immunity attenuated acute lung injury by activating alveolar macrophages via AKT2-PDK1 axis-mediated metabolic reprogramming.
| Τίτλος: | Trained immunity attenuated acute lung injury by activating alveolar macrophages via AKT2-PDK1 axis-mediated metabolic reprogramming. |
|---|---|
| Συγγραφείς: | Sun Z; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., Meng H; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., Wang X; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., Guo X; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., He W; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., Zhou Y; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., Wang Z; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., Li Z; Department of Pulmonary and Critical Care Medicine, Hebei Chest Hospital, Shijiazhuang, Hebei, China. li-zhsh@163.com.; Hebei Provincial Key Laboratory of Pulmonary Disease, Shijiazhuang, Hebei, China. li-zhsh@163.com., Li X; Department of Pulmonary and Critical Care Medicine, Hebei Chest Hospital, Shijiazhuang, Hebei, China. lixingbin@126.com.; Hebei Provincial Key Laboratory of Pulmonary Disease, Shijiazhuang, Hebei, China. lixingbin@126.com., Wang Y; Department of Pulmonary and Critical Care Medicine, Hebei Chest Hospital, Shijiazhuang, Hebei, China. yuanwang3389@163.com.; Hebei Provincial Key Laboratory of Pulmonary Disease, Shijiazhuang, Hebei, China. yuanwang3389@163.com. |
| Πηγή: | Journal of translational medicine [J Transl Med] 2025 Dec 23; Vol. 23 (1), pp. 1412. Date of Electronic Publication: 2025 Dec 23. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BioMed Central, 2003- |
| Ιατρικοί όροι (MeSH): | Macrophages, Alveolar*/metabolism , Macrophages, Alveolar*/immunology , Macrophages, Alveolar*/drug effects , Acute Lung Injury*/immunology , Acute Lung Injury*/pathology , Acute Lung Injury*/metabolism , Proto-Oncogene Proteins c-akt*/metabolism , Cellular Reprogramming*, Lipopolysaccharides/pharmacology ; Signal Transduction/drug effects ; beta-Glucans/pharmacology ; Glycolysis/drug effects ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism ; Lactic Acid/metabolism ; Animals ; Male ; Mice, Inbred C57BL ; Mice ; Metabolic Reprogramming ; Trained Immunity |
| Περίληψη: | Background: Acute lung injury (ALI) is a life-threatening clinical syndrome typically triggered by sepsis or severe trauma lacking effective treatment options. Alveolar macrophages (AMs), representing the most abundant immune cell population in pulmonary tissue, exhibited functional abnormalities that were closely associated with ALI pathogenesis. Notably, elevated pulmonary lactate secretion served not only as a characteristic pathological feature of ALI but also participated in disease progression through modulation of AMs activity. Trained immunity was found to activate innate immune cells including macrophages, regulating metabolic adaptations that alleviated ALI, though the precise mechanisms remained unclear. Methods: We used β-glucan and LPS to establish both in vivo and in vitro models of trained immunity and ALI, enabling investigation of trained immunity effects on AMs immunoregulatory functions. Results: The results demonstrated that trained immunity effectively attenuated ALI severity by up-regulating glycolytic activity in AMs, thereby potentiating their immune responsiveness, and primarily enabled alveolar macrophages to sustain immune responses in high-lactate environments through the AKT2-PDK1 axis, an effect that was abolished by relevant inhibitors. Conclusions: We concluded that β-glucan induced trained immunity could enhance alveolar macrophage immune activity and improve lactate metabolic tolerance, offering a novel therapeutic approach for acute lung injury (ALI). (© 2025. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: This study was carried out in accordance with the principles of the Basel Declaration and recommendations of the US NIH with Specific Pathogen Free conditions. The protocol was approved by the Model Animal Research Center of Nanjing University. All-time-available Standard rodent chow and water were also provided. Competing interests: The authors declare no competing interests. |
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| Grant Information: | 32200714 National Natural Science Foundation of China; 20220099 Henan Normal University; 2025001 Hebei Provincial Key Research Projects |
| Contributed Indexing: | Keywords: AKT2; Acute lung injury; Alveolar macrophages; Lactate; Pyruvate dehydrogenase kinase 1; Trained immunity |
| Substance Nomenclature: | EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (Lipopolysaccharides) 0 (beta-Glucans) 0 (Pyruvate Dehydrogenase Acetyl-Transferring Kinase) 33X04XA5AT (Lactic Acid) 0 (Pdk1 protein, mouse) |
| Entry Date(s): | Date Created: 20251223 Date Completed: 20251224 Latest Revision: 20260724 |
| Update Code: | 20260724 |
| PubMed Central ID: | PMC12723939 |
| DOI: | 10.1186/s12967-025-06879-4 |
| PMID: | 41437043 |
| Βάση Δεδομένων: | MEDLINE |
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