| Title: |
Myeloid cell-specific deletion of AMPKα1 worsens ocular bacterial infection by skewing macrophage phenotypes |
| Authors: |
Singh, Sukhvinder; Singh, Pawan Kumar; Ahmad, Zeeshan; Das, Susmita; Foretz, Marc; Viollet, Benoit; Giri, Shailendra; Kumar, Ashok |
| Contributors: |
Université Paris Cité (UPCité); Institut Cochin (IC UM3 (UMR 8104 / U1016)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Department of Experimental Pathology; Mayo Clinic; Department of Clinical Research, National Research Institute of Ayurveda Drug Development, Kolkata, India |
| Source: |
ISSN: 0022-1767. |
| Publisher Information: |
CCSD; Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists |
| Publication Year: |
2024 |
| Subject Terms: |
Eye; Endophthalmitis; S. aureus; Inflammation; AMPK; Immunometabolism; macrophages; MESH: Animals; MESH: Mice; MESH: Phagocytosis; MESH: Endophthalmitis; MESH: Eye Infections; Bacterial; MESH: AMP-Activated Protein Kinases; Knockout; MESH: Myeloid Cells; MESH: Macrophages; Inbred C57BL; MESH: Staphylococcus aureus; MESH: Staphylococcal Infections; MESH: Phenotype; [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Biochemistry [q-bio.BM]; [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Molecular biology; [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism |
| Description: |
International audience ; AMP-activated protein kinase (AMPK) plays a crucial role in governing essential cellular functions such as growth, proliferation, and survival. Previously, we observed increased vulnerability to bacterial (S. aureus) endophthalmitis in global AMPKα1 knockout (KO) mice. In this study, we investigated the specific involvement of AMPKα1 in myeloid cells using LysM Cre ; AMPKα1 fl mice. Our findings revealed that while endophthalmitis resolved in wild-type (WT) B6 mice, the severity of the disease progressively worsened in AMPKα1 deficient mice over time. Moreover, the intraocular bacterial load and inflammatory mediators (e.g., IL-1β, TNF-α, IL-6, and CXCL2) were markedly elevated in the LysM Cre ; AMPKα1 fl mice. Mechanistically, the deletion of AMPKα1 in myeloid cells skewed macrophage polarization toward the inflammatory M1 phenotype and impaired the phagocytic clearance of S. aureus by macrophages. Notably, transferring AMPKcompetent bone marrow from wild-type mice to AMPKα1 KO mice preserved retinal function and mitigated the severity of endophthalmitis. Overall, our study underscores the role of myeloid-specific AMPKα1 in promoting the resolution of inflammation in the eye during bacterial infection. Hence, therapeutic strategies aimed at restoring or enhancing AMPKα1 activity could improve visual outcomes in endophthalmitis and other ocular infections. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39413004; PUBMED: 39413004; PUBMEDCENTRAL: PMC11573643 |
| DOI: |
10.4049/jimmunol.2400282 |
| Availability: |
https://hal.science/hal-04792798; https://hal.science/hal-04792798v1/document; https://hal.science/hal-04792798v1/file/Singh%20et%20al%20AMPK%20Myleoid_05122024.pdf; https://doi.org/10.4049/jimmunol.2400282 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.B21CDA7C |
| Database: |
BASE |