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Mycobacterium bovis   BCG, a live attenuated strain of   M. bovis   initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK) cells. In that context, we aimed to study the impact of   M. bovis   BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that   M. bovis   BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56 bright  NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56 bright  population. In summary, we observed that   M. bovis   BCG is modulating the functions of CD56 bright  NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56 bright  cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for   M. bovis   BCG as an immunotherapeutic agent.

plos one

Natural Killer Cell Cytokine Response to M. bovis BCG Is Associated with Inhibited Proliferation, Increased Apoptosis and Ultimate Depletion of NKp44+CD56bright Cells