Inhibition of the PI3K-Akt-mTOR signaling pathway in T lymphocytes in patients with active tuberculosis

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.

Keywords

• PI3K-Akt-mTOR pathway
• T lymphocytes
• FoxP3+Treg cells
• Mycobacterium tuberculosis