mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections
| Autor: | Wei Guo, Qian Wan, Xiaoyan Zhang, Fei Yang, Shixuan Wang, Huaijun Tu, Jian Li, Li-Jun Fang, Xulong Zhan, Ting Xue, Zhexin Shi, Yazhi Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Cell type Article Subject T cell Immunology Regulator mTORC1 Biology Mechanistic Target of Rapamycin Complex 1 T-Lymphocytes Regulatory Monocytes 03 medical and health sciences Mice 0302 clinical medicine Immune system Transforming Growth Factor beta medicine Escherichia coli lcsh:Pathology Animals PI3K/AKT/mTOR pathway Mice Knockout Innate immune system Effector Interleukin-6 Tumor Necrosis Factor-alpha TOR Serine-Threonine Kinases Cell Biology Bacterial Infections Interleukin-10 030104 developmental biology medicine.anatomical_structure Multiprotein Complexes Female 030215 immunology Research Article Interleukin-1 lcsh:RB1-214 |
| Zdroj: | Mediators of Inflammation, Vol 2016 (2016) Mediators of Inflammation |
| ISSN: | 0962-9351 |
| DOI: | 10.1155/2016/7369351 |
| Popis: | The TSC1/2 heterodimer, a key upstream regulator of the mTOR, can inhibit the activation of mTOR, which plays a critical role in immune responses after bacterial infections. Monocytes are an innate immune cell type that have been shown to be involved in bacteremia. However, how the mTOR pathway is involved in the regulation of monocytes is largely unknown. In our study, TSC1 KO mice and WT mice were infected withE. coli. When compared to WT mice, we found higher mortality, greater numbers of bacteria, decreased expression of coactivators in monocytes, increased numbers of Tregs, and decreased numbers of effector T cells in TSC1 KO mice. Monocytes obtained from TSC1 KO mice produced more ROS, IL-6, IL-10, and TGF-βand less IL-1, IFN-γ, and TNF-α. Taken together, our results suggest that the inhibited immune functioning in TSC1 KO mice is influenced by mTORC1 activation in monocytes. The reduced expression of coactivators resulted in inhibited effector T cell proliferation. mTORC1-activated monocytes are harmful during bacterial infections. Therefore, inhibiting mTORC1 signaling through rapamycin administration could rescue the harmful aspects of an overactive immune response, and this knowledge provides a new direction for clinical therapy. |
| Databáze: | OpenAIRE |
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