Decreased IL-17 during treatment of sputum smear-positive pulmonary tuberculosis due to increased regulatory T cells and IL-10

Background: Tuberculosis (TB) remains a major public health concern worldwide. Previous studies have demonstrated that IL-17 plays an important role in initial immune response and is involved in both immune-mediated protection and pathology following infection with Mycobacterium tuberculosis (MTB). However, the alterations and regulation of plasma IL-17 level during TB treatment remain unclear. Moreover, the cell type responsible for the production of IL-17 in TB patients requires further study. Methods: A total of 20 acid-fast bacilli smear-positive (AFB-positive) pulmonary TB patients and 20 age-and gender-matched healthy volunteers were included in our study. Blood samples were collected in heparinized tubes at the time of diagnosis (AFB-positive group) and 3 weeks after the initiation of therapy, when the sputum smear conversion (AFB-negative group) occurred, followed by symptomatic improvement. IL-17 levels and IL-17-producing cells in PBMCs were detected. Lymphocyte populations in the peripheral blood between the AFB-positive and AFB-negative groups were compared by flow-cytometry. A549 cells, a cell line of alveolar epithelial cells, were applied to determine the extent of the pathological damage mediated by IL-17 following MTB infection. Recombinant human IL-10 was used to investigate the regulation of IL-17 expression after sputum smear conversion in AFB-positive pulmonary TB patients. Results: Plasma IL-17 level were elevated in patients with sputum AFB-positive pulmonary TB, but substantially decreased after TB treatment and smear conversion. Our data indicate that NKT-like cells might be the main source of IL-17, in addition to conventional T cells in AFB-positive pulmonary TB patients. The secretion of IL-17 may be suppressed by regulatory T (Treg) cells and IL-10 during TB treatment. Moreover, the IL-17 levels were positively correlated to both the C-reactive protein and erythrocyte sedimentation rate. Therefore, IL-17 was capable of alveolar epithelial cell damage following MTB infection. Conclusion: The increase in the frequency of Treg cells and IL-10 levels was associated with a decrease in IL-17 in patients receiving TB treatment. Thus, IL-10 and Tregs may function to inhibit immune-mediated pathology in TB patients.