XueXuan Zhang1, TengYi Huang1, Ying Wu1, WenGuang Peng2, HanBin Xie2, MeiChen Pan1, HuanBin Zhou1, BoZhi Cai3, YingE Wu4. 1. Department of Laboratory Medicine, The First Affiliated Hospital of Shantou University Medical College, Chang Ping Road, 57, Shantou, Guangdong 515041, China. 2. Department of Thoracic Medicine, The Third People's Hospital of Shantou City, Guangdong, China. 3. Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. 4. Department of Laboratory Medicine, The First Affiliated Hospital of Shantou University Medical College, Chang Ping Road, 57, Shantou, Guangdong 515041, China. Electronic address: yinge_wu@126.com.
Abstract
OBJECTIVES: To investigate PI3K-Akt-mTOR signaling pathway changes and the proliferation of FoxP3+Treg cells in patients with active tuberculosis. METHODS: We isolated PBMCs and CD4+CD25+FoxP3+Treg cells from peripheral blood collected from patients with active tuberculosis and healthy controls. We compared the proportion and MFI of PI3K-Akt-mTOR pathway components and PTEN by flow cytometry using specific cell-surface and intracellular markers. Moreover, we detected the specific secretory proteins ESAT-6 and Ag85B, cytokines IL-10, TGF-β1 and IL-35 in serum by ELISA. RESULTS: Compared with healthy controls, the proportions of CD3+Akt+, CD3+p-Akt+, CD3+mTOR+, CD3+p-mTOR+ and CD3+PTEN+ cells, in the T lymphocyte population of patients with active tuberculosis, were decreased (p<0.05), while CD3+FoxP3+ cells were increased (p=0.013). Similarly, for CD4+CD25+FoxP3+Treg cells, the proportions of Akt+ cells, p-Akt+ cells, mTOR+ cells, p-mTOR+ cells and PTEN+ cells were decreased (p<0.05) in patients with active tuberculosis. Compared with healthy controls, the levels of ESAT-6 and Ag85B were higher in patients with active tuberculosis (p<0.001). Levels of IL-10 and TGF-β1 were higher (p<0.001), whereas the level of IL-35 was lower (p<0.001). CONCLUSION: The PI3K-Akt-mTOR signaling pathway in T lymphocytes and CD4+CD25+FoxP3+Treg cells was inhibited, which could explain why M.tuberculosis can induce FoxP3+Treg cell to expand.
OBJECTIVES: To investigate PI3K-Akt-mTOR signaling pathway changes and the proliferation of FoxP3+Treg cells in patients with active tuberculosis. METHODS: We isolated PBMCs and CD4+CD25+FoxP3+Treg cells from peripheral blood collected from patients with active tuberculosis and healthy controls. We compared the proportion and MFI of PI3K-Akt-mTOR pathway components and PTEN by flow cytometry using specific cell-surface and intracellular markers. Moreover, we detected the specific secretory proteins ESAT-6 and Ag85B, cytokines IL-10, TGF-β1 and IL-35 in serum by ELISA. RESULTS: Compared with healthy controls, the proportions of CD3+Akt+, CD3+p-Akt+, CD3+mTOR+, CD3+p-mTOR+ and CD3+PTEN+ cells, in the T lymphocyte population of patients with active tuberculosis, were decreased (p<0.05), while CD3+FoxP3+ cells were increased (p=0.013). Similarly, for CD4+CD25+FoxP3+Treg cells, the proportions of Akt+ cells, p-Akt+ cells, mTOR+ cells, p-mTOR+ cells and PTEN+ cells were decreased (p<0.05) in patients with active tuberculosis. Compared with healthy controls, the levels of ESAT-6 and Ag85B were higher in patients with active tuberculosis (p<0.001). Levels of IL-10 and TGF-β1 were higher (p<0.001), whereas the level of IL-35 was lower (p<0.001). CONCLUSION: The PI3K-Akt-mTOR signaling pathway in T lymphocytes and CD4+CD25+FoxP3+Treg cells was inhibited, which could explain why M.tuberculosis can induce FoxP3+Treg cell to expand.
Authors: Wen-Ping Gong; Yan Liang; Yan-Bo Ling; Jun-Xian Zhang; You-Rong Yang; Lan Wang; Jie Wang; Ying-Chang Shi; Xue-Qiong Wu Journal: Mil Med Res Date: 2020-06-03