| First Author | Singh S | Year | 2024 |
| Journal | J Immunol | Volume | 213 |
| Issue | 11 | Pages | 1656-1665 |
| PubMed ID | 39413004 | Mgi Jnum | J:359873 |
| Mgi Id | MGI:7782837 | Doi | 10.4049/jimmunol.2400282 |
| Citation | Singh S, et al. (2024) Myeloid Cell-Specific Deletion of AMPKalpha1 Worsens Ocular Bacterial Infection by Skewing Macrophage Phenotypes. J Immunol 213(11):1656-1665 |
| abstractText | 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 (Staphylococcus aureus) endophthalmitis in global AMPKalpha1 knockout mice. In this study, we investigated the specific involvement of AMPKalpha1 in myeloid cells using LysMCre;AMPKalpha1fl mice. Our findings revealed that whereas endophthalmitis resolved in wild-type C57BL/6 mice, the severity of the disease progressively worsened in AMPKalpha1-deficient mice over time. Moreover, the intraocular bacterial load and inflammatory mediators (e.g., IL-1beta, TNF-alpha, IL-6, and CXCL2) were markedly elevated in the LysMCre;AMPKalpha1fl mice. Mechanistically, the deletion of AMPKalpha1 in myeloid cells skewed macrophage polarization toward the inflammatory M1 phenotype and impaired the phagocytic clearance of S. aureus by macrophages. Notably, transferring AMPK-competent bone marrow from wild-type mice to AMPKalpha1 knockout mice preserved retinal function and mitigated the severity of endophthalmitis. Overall, our study underscores the role of myeloid-specific AMPKalpha1 in promoting the resolution of inflammation in the eye during bacterial infection. Hence, therapeutic strategies aimed at restoring or enhancing AMPKalpha1 activity could improve visual outcomes in endophthalmitis and other ocular infections. |
