NK cells inhibit anti-Mycobacterium bovis BCG T cell responses and aggravate pulmonary inflammation in a direct lung infection mouse model.

Tuberculosis remains a threat to public health. The major problem for curing this disease is latent infection, of which the underlying mechanisms are still not fully understood. Previous studies indicate that natural killer (NK) cells do not play a role in inhibiting the growth of Mycobacterium tuberculosis in the lung, and recent studies have revealed that NK cells regulate the adaptive immunity during mycobacterial infection. By using a mouse model of direct lung infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG), we found that the presence of NK cells postponed the priming and activation of T cells after BCG infection. In addition, depletion of NK cells before infection alleviated pulmonary pathology. Further studies showed that NK cells lysed BCG-infected macrophages in an NKG2D dependent manner. Thus, NK cells did not play a direct role in control BCG, but aggravated the pulmonary inflammation and impaired anti-BCG T cell immunity, likely through killing BCG-infected macrophages. Our results may have important implications for the design of immune therapy to treat tuberculosis.