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

•We mainly study the change of PI3K-Akt-mTOR signaling pathway in T lymphocytes and Treg cells from active TB patients.•The results showed that the mTOR signaling pathway in T lymphocytes and Treg cells is inhibited in active TB patients.•The mTOR pathway is inhibited in active TB patients, which could explain why FoxP3 expanded in patients in partly.

SummaryObjectivesTo investigate PI3K-Akt-mTOR signaling pathway changes and the proliferation of FoxP3+Treg cells in patients with active tuberculosis.MethodsWe 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.ResultsCompared 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).ConclusionThe 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.