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Extracellular vesicles from alveolar macrophages harboring phagocytosed methicillin-resistant Staphylococcus aureus induce necroptosis.
Bai, Songjie; Wen, Xuehuan; Li, Bingyu; Hu, Ruomeng; Yang, Jie; Yu, Qing; Zeng, Xianchang; Feng, Huajun; Zhu, Feng; Cai, Zhijian; Zhang, Gensheng.
Afiliación
  • Bai S; Department of Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Wen X; Department of Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Li B; Department of Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Hu R; Department of Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Yang J; Department of Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Yu Q; Department of Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Zeng X; Institute of Immunology, and Department of Orthopedics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Feng H; Ecological-Environment & Health College (EEHC), Zhejiang A&F University, Hangzhou, Zhejiang 311300, China. Electronic address: fenghuajun@zafu.edu.cn.
  • Zhu F; Department of Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China. Electronic address: alexzhujunchi@hotmail.com.
  • Cai Z; 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.
  • Zhang G; 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
Cell Rep ; 43(7): 114453, 2024 Jul 23.
Article en En | MEDLINE | ID: mdl-38985677
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Macrófagos Alveolares / MicroARNs / Staphylococcus aureus Resistente a Meticilina / Vesículas Extracelulares / Necroptosis Límite: Animals / Humans / Male Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Macrófagos Alveolares / MicroARNs / Staphylococcus aureus Resistente a Meticilina / Vesículas Extracelulares / Necroptosis Límite: Animals / Humans / Male Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos