Myeloid Cell–Specific Deletion of AMPKα1 Worsens Ocular Bacterial Infection by Skewing Macrophage Phenotypes - Archive ouverte HAL
Article Dans Une Revue Journal of Immunology Année : 2024

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

Sukhvinder Singh
  • Fonction : Auteur
Pawan Kumar Singh
Zeeshan Ahmad
  • Fonction : Auteur
Susmita Das
  • Fonction : Auteur
Marc Foretz
Benoit Viollet
Shailendra Giri
Ashok Kumar
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-04791780 , version 1 (19-11-2024)

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Citer

Sukhvinder Singh, Pawan Kumar Singh, Zeeshan Ahmad, Susmita Das, Marc Foretz, et al.. Myeloid Cell–Specific Deletion of AMPKα1 Worsens Ocular Bacterial Infection by Skewing Macrophage Phenotypes. Journal of Immunology, 2024, 213 (11), pp.1656-1665. ⟨10.4049/jimmunol.2400282⟩. ⟨hal-04791780⟩

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