Mycobacterium Tuberculosis (Mtb) Antigen-Induced Upregulation Of Interleukin-35 Expression In Patients With Mtb Infection: In Vitro Blockade Of The Effects Of Interleukin-35 On T Lymphocyte Subsets

Immunosuppressive interleukin-35 (IL-35) serum concentrations were analyzed in patients with active pulmonary Mycobacterium tuberculosis (MTB) infections (PTB), PTB patients after two months treatment (stable PTB) and healthy controls. IL-35 concentrations were highest in active PTB followed by stable PTB cases and lowest in healthy control participants (all P < 0.01). The same trents were found for supernatants of isolated blood mononuclear cells (PBMCs), with additional enhancements after MTB antigen stimulation only for PBMCs of active and stable PTB patients (P < 0.001), for EBI3 and IL-12a transcriptions in PBMCs (P < 0.001) and percentages of EBI3 expressing (CD4 + CD25 + Foxp3+) regulatory T cells (Treg) (P < 0.001). IL-35 antibody applications significantly reversed MTB antigen stimulated IL-35 and IL-10 expression in PBMCs of active and stable PTB patients, and reduced Foxp3 expression in CD4 + CD25 + cells and EBI3 expression in Treg cells, but had no effects on healthy control cells. The percentages of Th1 and Th17 cells in CD4 + cells were enhanced after MTB antigen stimulation of cells taken from active and stable PTB patients, which were partly increased only for Th1 cells after IL-35 antibody exposure. MTB antigen-driven upregulation of IL-35 may lead to reduced immune surveillance in PTB patients.