Myeloid Cell-Specific Deletion of AMPKα1 Worsens Ocular Bacterial Infection by Skewing Macrophage Phenotypes.

Document Type

Article

Publication Date

12-1-2024

Publication Title

Journal of immunology (Baltimore, Md. : 1950)

Abstract

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 AMPKα1 knockout mice. In this study, we investigated the specific involvement of AMPKα1 in myeloid cells using LysMCre;AMPKα1fl mice. Our findings revealed that whereas endophthalmitis resolved in wild-type C57BL/6 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 LysMCre;AMPKα1fl 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 AMPK-competent bone marrow from wild-type mice to AMPKα1 knockout 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.

Medical Subject Headings

Animals; Mice; AMP-Activated Protein Kinases; Mice, Knockout; Myeloid Cells; Macrophages; Mice, Inbred C57BL; Staphylococcus aureus; Staphylococcal Infections; Phenotype; Phagocytosis; Endophthalmitis; Eye Infections, Bacterial

PubMed ID

39413004

ePublication

ePub ahead of print

Volume

213

Issue

11

First Page

1656

Last Page

1665

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