Different immunosuppressive mechanisms in multi‐drug‐resistant tuberculosis and non‐tuberculous mycobacteria patients
Previous studies have demonstrated that cells from both multi‐drug‐resistant tuberculosis (MDR‐TB) and non‐tuberculous mycobacteria (NTM) patients respond poorly to mycobacterial antigens in vitro. In the present study, we compared the in vitro response of cells isolated from sensitive TB (NR‐TB)‐, MDR‐TB‐ and NTM‐infected patients. Analysis of T cell phenotype ex vivo revealed that both MDR‐TB and NTM patients present an increased percentage of CD4+CD25+‐ forkhead box protein 3 (FoxP3)+ and CD4+CD25+CD127− regulatory T (Treg) cells when compared to NR‐TB. Increased numbers of Treg cells and interleukin (IL)‐10 serum levels were detected in MDR‐TB, whereas elevated serum transforming growth factor (TGF)‐β was found in the NTM group. Cells of MDR‐TB patients stimulated with early secretory antigenic target (ESAT)‐6, but not purified protein derivative (PPD), showed a lower frequency of CD4+/interferon (IFN)‐γ+ T cells and enhanced CD4+CD25+FoxP3+, CD4+CD25+CD127− and CD4+CD25+IL‐10+ T cell population. In addition, increased IL‐10 secretion was observed in cultured MDR‐TB cells following ESAT‐6 stimulation, but not in NR‐TB or NTM patients. In vitro blockade of IL‐10 or IL‐10Rα decreased the CD4+CD25+FoxP3+ frequencies induced by ESAT‐6 in MDR‐TB, suggesting a role of IL‐10 on impaired IFN‐γ responses seen in MDR‐TB. Depletion of CD4+CD25+ T lymphocytes restored the capacity of MDR‐TB T cells to respond to ESAT‐6 in vitro, which suggests a potential role for Treg/T regulatory 1 cells in the pathogenesis of MDR‐TB. Together, our results indicate that although the similarities in chronicity, NTM‐ and MDR‐TB‐impaired antigenic responses involve different mechanisms.