title: mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections.
abstract: 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.
authors.affiliation: Department of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, China; Medical Department of Nanchang University Graduate School, Nanchang, Jiangxi, China.
authors.forename: Lijun
authors.identifier: 0000-0002-2653-9034
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Huaijun
authors.initials: H
authors.lastname: Tu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, China; Medical Department of Nanchang University Graduate School, Nanchang, Jiangxi, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, China; Medical Department of Nanchang University Graduate School, Nanchang, Jiangxi, China.
authors.forename: Yazhi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, China; Medical Department of Nanchang University Graduate School, Nanchang, Jiangxi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wan
authors.affiliation: Department of Hematology and Oncology, The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Zhexin
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, China; Medical Department of Nanchang University Graduate School, Nanchang, Jiangxi, China.
authors.forename: Xulong
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Department of Hematology, The Second Affiliated Hospital of Nanchang University, Key Laboratory of Experimental Hematology in Jiangxi Province, Nanchang, Jiangxi, China.
authors.forename: Jian
authors.identifier: 0000-0003-2396-5342
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology* / Q000378:metabolism*; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D046912:Multiprotein Complexes; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases