Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages

Purpose: This study aimed to explore the effect of Rapamycin (Rapa) in Staphylococcus aureus (S. aureus) pneumonia and clarify its possible mechanism. Methods: We investigated the effects of Rapa on S. aureus pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms wer...

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Bibliographic Details
Published in:Journal of inflammation research 2023-12, Vol.16, p.5715-5728
Main Authors: Yu, Fang-Yi, Zheng, Kua, Wu, Yin-Fang, Gao, Shen-Wei, Weng, Qing-Yu, Zhu, Chen, Wu, Yan-Ping, Li, Miao, Qin, Zhong-Nan, Lou, Jia-Fei, Chen, Zhi-Hua, Ying, Song-Min, Shen, Hua-Hao, Li, Wen
Format: Article
Language:English
Subjects:
Bacterial pneumonia
Cytokines
Inflammation
macrophage
Macrophages
mtor- ribosomal protein s6 signaling pathway
Original Research
Pneumonia
Rapamycin
Staphylococcus aureus
Staphylococcus aureus infections
Type 2 diabetes
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Summary:Purpose: This study aimed to explore the effect of Rapamycin (Rapa) in Staphylococcus aureus (S. aureus) pneumonia and clarify its possible mechanism. Methods: We investigated the effects of Rapa on S. aureus pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms were investigated: the mTOR-RPS6 pathway phosphorylation and phagocytosis. Furthermore, for the mechanism verification in vivo, mice with specific Mtor knockout in myeloid cells were constructed for pneumonia models. Results: Rapa exacerbated S. aureus pneumonia in mouse models, promoting chemokines secretion and inflammatory cells infiltration in lung. In vitro, Rapa upregulated the secretion of chemokines and cytokines in macrophages induced by S. aureus. Mechanistically, the mTOR-ribosomal protein S6 (RPS6) pathway in macrophages was phosphorylated in response to S. aureus infection, and the inhibition of RPS6 phosphorylation upregulated the inflammation level. However, Rapa did not increase the phagocytic activity. Accordingly, mice with specific Mtor knockout in myeloid cells experienced more severe S. aureus pneumonia. Conclusion: Rapa exacerbates S. aureus pneumonia by increasing the inflammatory levels of macrophages. Inhibition of mTOR-RPS6 pathway upregulates the expression of cytokines and chemokines in macrophages, thus increases inflammatory cells infiltration and exacerbates tissue damage. Keywords: Staphylococcus aureus, pneumonia, macrophage, rapamycin, mTOR- ribosomal protein S6 signaling pathway
ISSN:1178-7031
1178-7031
DOI:10.2147/JIR.S434483