Metformin improves Mycobacterium avium infection by strengthening macrophage antimicrobial functions

Three weeks of metformin treatment significantly reduced the lung mycobacterial burden in mice infected with Mav without major changes in the overall lung pathology or immune cell composition. Metformin treatment had no significant impact on tissue inflammation except for a tendency of increased lung IFNγ and infiltration of Mav-specific IFNγ-secreting T cells. Metformin did, however, boost the antimicrobial capacity of infected macrophages directly by modulating metabolism/activating AMPK, increasing mitochondrial ROS and phagosome maturation, and indirectly by bolstering type I immunity. Taken together, our data show that metformin improved the control of Mav-infection in mice, mainly by strengthening antimicrobial defenses in macrophages, and suggest that metformin has potential as an adjunct treatment of Mav infections.