mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections
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 i...
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doaj-af42f8948f954f28992bc31396cc26e02020-11-25T00:34:42ZengHindawi LimitedMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/73693517369351mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial InfectionsLijun Fang0Huaijun Tu1Wei Guo2Shixuan Wang3Ting Xue4Fei Yang5Xiaoyan Zhang6Yazhi Yang7Qian Wan8Zhexin Shi9Xulong Zhan10Jian Li11Department of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, ChinaDepartment of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin, ChinaDepartment of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin, ChinaDepartment of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, ChinaDepartment of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, ChinaDepartment of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, ChinaDepartment of Hematology and Oncology, The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaDepartment of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, ChinaDepartment of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, ChinaThe 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 with E. 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-β and 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.http://dx.doi.org/10.1155/2016/7369351 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lijun Fang Huaijun Tu Wei Guo Shixuan Wang Ting Xue Fei Yang Xiaoyan Zhang Yazhi Yang Qian Wan Zhexin Shi Xulong Zhan Jian Li |
spellingShingle |
Lijun Fang Huaijun Tu Wei Guo Shixuan Wang Ting Xue Fei Yang Xiaoyan Zhang Yazhi Yang Qian Wan Zhexin Shi Xulong Zhan Jian Li mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections Mediators of Inflammation |
author_facet |
Lijun Fang Huaijun Tu Wei Guo Shixuan Wang Ting Xue Fei Yang Xiaoyan Zhang Yazhi Yang Qian Wan Zhexin Shi Xulong Zhan Jian Li |
author_sort |
Lijun Fang |
title |
mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections |
title_short |
mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections |
title_full |
mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections |
title_fullStr |
mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections |
title_full_unstemmed |
mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections |
title_sort |
mtorc1-activated monocytes increase tregs and inhibit the immune response to bacterial infections |
publisher |
Hindawi Limited |
series |
Mediators of Inflammation |
issn |
0962-9351 1466-1861 |
publishDate |
2016-01-01 |
description |
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 with E. 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-β and 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. |
url |
http://dx.doi.org/10.1155/2016/7369351 |
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