The attenuation of Th1 and Th17 responses via autophagy protects against methicillin-resistant Staphylococcus aureus-induced sepsis |
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| Institution: | 1. Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Cardiovascular Key Lab of Zhejiang Province, Hangzhou, Zhejiang 310009, China;2. Department of Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China;3. Department of Emergency Medicine, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China;4. Clinical Microbiology Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China;5. Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou 310058, China;6. Clinical Research Center, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang 510004, China;1. Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;2. School of Medicine, National Yang-Ming University, Taipei, Taiwan;3. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan;4. Institute of Public Health, National Yang-Ming University, Taipei, Taiwan;5. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;6. Division of Cerebrovascular Diseases, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan;7. Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan;8. Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan;1. Purdue Institute of Inflammation, Immunology and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA;2. State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian Province, 361102, China;1. Institute of Cytology, RAS, St Petersburg, Russia;2. Institute of Molecular Genetics of National Research Center “Kurchatov Institute”, RAS, Moscow, Russia;3. Demidov Yaroslavl State University, Yaroslavl, Russia |
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| Abstract: | Whether autophagy affects methicillin-resistant Staphylococcus aureus (MRSA)-induced sepsis and the associated mechanisms are largely unknown. This study investigated the role of autophagy in MRSA-induced sepsis. The levels of microtubule-associated protein light chain 3 (LC3)-II/I, Beclin-1 and p62 after USA300 infection were examined by Western blotting and immunohistochemical staining. Bacterial burden analysis, hematoxylin-eosin staining, and Kaplan–Meier analysis were performed to evaluate the effect of autophagy on MRSA-induced sepsis. IFN-γ and IL-17 were analyzed by ELISA, and CD4+ T cell differentiation was assessed by flow cytometry. Our results showed that LC3-II/I and Beclin-1 were increased, while p62 was decreased after infection. Survival rates were decreased in the LC3B−/− and Beclin-1+/− groups, accompanied by worsened organ injuries and increased IFN-γ and IL-17 levels, whereas rapamycin alleviated organ damage, decreased IFN-γ and IL-17 levels, and improved the survival rate. However, there was no significant difference in bacterial burden. Flow cytometric analysis showed that rapamycin treatment decreased the frequencies of Th1 and Th17 cells, whereas these cells were upregulated in the LC3B−/− and Beclin-1+/− groups. Therefore, autophagy plays a protective role in MRSA-induced sepsis, which may be partly associated with the alleviation of organ injuries via the downregulation of Th1 and Th17 responses. These results provide a nonantibiotic treatment strategy for sepsis. |
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| Keywords: | Autophagy MRSA Th1 Th17 |
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