Mycobacterial growth control is heterogeneous but maintained during treatment in patients with tuberculosis disease

Tuberculosis (TB) is a curable infectious disease that requires prolonged treatment with multiple antibiotics. To better understand how the immune system contributes to the clearance of Mycobacterium tuberculosis (Mtb), in vitro assays are essential for monitoring functional immune changes during infection, therapy, and following vaccination. In this study, we investigated whether mycobacterial growth control in thirty patients with TB disease changes over the course of treatment. Comprehensive immune profiling of peripheral blood mononuclear cells (PBMCs), using a 30-color spectral flow cytometry panel, identified dynamic shifts in immune cell subsets related to functional activity. Notably, in addition to memory and effector T cells, a subset of naive B cells changed during treatment. Most sera contained antibodies binding to purified protein derivative (PPD) and Mtb-specific antigens ESAT-6/CFP-10, and enhanced phagocytic activity. A functional mycobacterial growth inhibition assay (MGIA) revealed growth control, which appeared to be heterogeneous but generally sustained throughout longitudinal follow-up. We conclude that T and B cell responses change in response to antibiotic treatment of TB disease, but that mycobacterial growth control capacity is a property of the individual, which is not influenced by disease activity or antibiotic treatment.