The attenuation of Th1 and Th17 responses via autophagy protects against methicillin-resistant Staphylococcus aureus-induced sepsis.

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.

• Authors: Shufang Zhang, Xiaofang Huang, Huiqing Xiu, Zhongheng Zhang, Kai Zhang, Jiachang Cai, Zhijian Cai, Zhanghui Chen, Zhaocai Zhang, Wei Cui, Gensheng Zhang, Meixiang Xiang
• Journal: Microbes and infection (Microbes Infect) 2021 Sep-Oct Vol. 23 Issue 8 Pg. 104833 ISSN: 1769-714X [Electronic] France
• PMID: 33930602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Beclin-1
• Interleukin-17
• Microtubule-Associated Proteins
• Sirolimus

Topics

• Autophagy
• Beclin-1 (pharmacology)
• Humans
• Interleukin-17 (pharmacology)
• Methicillin-Resistant Staphylococcus aureus
• Microtubule-Associated Proteins
• Sepsis
• Sirolimus (pharmacology)
• Th1 Cells
• Th17 Cells