2. Academic Validation
  3. Extracellular vesicles from alveolar macrophages harboring phagocytosed methicillin-resistant Staphylococcus aureus induce necroptosis

Extracellular vesicles from alveolar macrophages harboring phagocytosed methicillin-resistant Staphylococcus aureus induce necroptosis

  • Cell Rep. 2024 Jul 23;43(7):114453. doi: 10.1016/j.celrep.2024.114453.
Songjie Bai 1,  Xuehuan Wen 1,  Bingyu Li 1,  Ruomeng Hu 1,  Jie Yang 1,  Qing Yu 1,  Xianchang Zeng 2,  Huajun Feng 3,  Feng Zhu 4,  Zhijian Cai 5,  Gensheng Zhang 6
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • 2 Institute of Immunology, and Department of Orthopedics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • 3 Ecological-Environment & Health College (EEHC), Zhejiang A&F University, Hangzhou, Zhejiang 311300, China. Electronic address: fenghuajun@zafu.edu.cn.
  • 4 Department of Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China. Electronic address: alexzhujunchi@hotmail.com.
  • 5 Institute of Immunology, and Department of Orthopedics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China. Electronic address: caizj@zju.edu.cn.
  • 6 Department of Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Hangzhou, Zhejiang 310009, China. Electronic address: genshengzhang@zju.edu.cn.
PMID: 38985677 DOI: 10.1016/j.celrep.2024.114453
Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) Infection, a major cause of hospital- and community-acquired pneumonia, still has a high mortality rate. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, have a significant impact on infectious diseases. However, the role of EVs from alveolar macrophages (AMs) in MRSA pneumonia remains unclear. We report that AMs phagocytose MRSA and release more EVs in mice with MRSA pneumonia. EVs from AMs harboring phagocytosed MRSA exhibit significant proinflammatory effects and induce Necroptosis by delivering tumor necrosis factor α (TNF-α) and miR-146a-5p. Mechanically, the upregulated miR-146a-5p in these EVs enhances the phosphorylation of RIPK1, RIPK3, and MLKL by targeting TNF receptor-associated factor 6 (TRAF6), thereby promoting TNF-α-induced Necroptosis. The combination of a TNF-α antagonist and an miR-146a-5p antagomir effectively improves the outcomes of mice with MRSA pneumonia. Overall, we reveal the pronecrotic effect of EVs from MRSA-infected AMs and provide a promising target for the prevention and treatment of MRSA pneumonia.

Keywords

CP: Immunology; CP: Microbiology; alveolar macrophages; extracellular vesicles; methicillin-resistant Staphylococcus aureus; miR-146a-5p; necroptosis.

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