Regulatory relationship between macrophage autophagy and PVL-positive methicillin-resistant Staphylococcus aureus |
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| Affiliation: | 1. Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei City 230022, Anhui Province, China;2. Department of Microbiology, Anhui Medical University, 69 Meishang Road, Shushan District, Hefei City 230032, Anhui Province, China;1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, 200025 Shanghai, China;2. Pôle de Recherches Sino-Français en Science du Vivant et Génomique, 197 Rui Jin Er Road, 200025 Shanghai, China;3. CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38700 La Tronche, France;1. Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark;2. National Veterinary Institute, Technical University of Denmark, Kgs. Lyngby, Denmark;3. Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark;4. Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark;5. Faculty of Veterinary Medicine, Ghent University, Belgium;1. Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China;2. Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China;3. National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China;4. International Joint Research Center on Cell Stress and Disease Diagnosis and Therapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China;1. Tianjin Medical University, Tianjin 300070, China;2. Department of Tissue Repair and Regeneration, PLA General Hospital and PLA Medical College, Beijing 100853, China;4. PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing 100048, China;5. Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing 100048, China;6. Plastic and Maxillofacial Surgery Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China;1. Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), Rua Dr. Bacelar 902, CEP 04057-000, São Paulo, SP, Brazil;2. Faculdade de Medicina da Universidade Federal de Alagoas, Campus A. C. Simões Tabuleiro do Martins, CEP 57072-900, Maceió, AL, Brazil;3. Departamento de Fisiopatologia, Instituto Butantan, Av. Vital Brasil 1500, CEP 05503-900, São Paulo, SP, Brazil;4. Pesquisadora associada, Pós-Doutoranda da Companhia Ambiental do Estado de São Paulo - CETESB, Brazil;1. Department of Pediatrics, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China;2. Department of Pediatrics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China;3. Department of Pediatrics, Jinling Hospital, the First School of Clinical Medicine, Southern Medical University, Nanjing 210093, Jiangsu, China;4. Department of Pediatrics, Jinling Hospital, Nanjing Medical University, Nanjing 210093, Jiangsu, China |
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| Abstract: | The present study intends to clarify the hypothesis that PVL-positive Methicillin-resistant S. aureus strain (PVL+-MRSA)-infected macrophages regulate autophagy and thus in turn inhibit phagocytosis through the in vitro and in vivo experiments. The autophagy of mouse macrophage cell line RAW264.7 was observed by fluorescence microscopy, and counted based on the number of each cell dot-like structure GFP-LC3. The protein levels of the phagocytic factors associated with autophagy were determined by western blotting. The phagocytosis of RAW264.7 on MRSA was determined by counting the colony. The clinically isolated and identified PVL+-MRSA strain was used to infect BALB/c mice (left nasal drip) to establish a mouse pneumonia model. PVL+-MRSA mice were then treated with 3-MA or linezolid. Bronchoalveolar lavage fluid (BALF) from mice was collected for macrophage counting by Flow cytometry assay. The right lung was aseptically isolated for counting the amount of bacteria. The results showed that PVL+-MRSA could induced the autophagy of macrophages, which in turn reduced the damage from macrophages, which were respectively alleviated by 3-MA and aggravated by rapamycin. Exogenous rPVL administrated into PVL--MRSA-infected macrophages caused the autophagy of macrophage. Exogenous rPVL, particularly A-Luk S-PV, administrated into macrophages also caused the autophagy of macrophage, which was reversed by PMX53, a C5aR antagonist. In a mouse pneumonia model, PVL+-MRSA could induced the autophagy of macrophages, which in turn reduced the damage from macrophages, which were respectively alleviated by 3-MA or linezolid. In conclusion, this study indicated PVL+-MRSA regulated macrophage autophagy, which in turns inhibit the phagocytosis of S. aureus by macrophage. This study may provide a potential target against S. aureus infection. |
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| Keywords: | Macrophage RAW264.7 Panton-Valentine leucocidin Autophagy |
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