SON DNA-binding protein mediates macrophage autophagy and responses to intracellular infection

Intracellular pathogens affect diverse host cellular defence and metabolic pathways. Here, we used infection withFrancisella tularensisto identify SON DNA-binding protein as a central determinant of macrophage activities. RNAi knockdown ofSONincreases survival of human macrophages followingF. tularensisinfection or inflammasome stimulation. SON is required for macrophage autophagy, interferon response factor 3 expression, type I interferon response and inflammasome-associated readouts.SONknockdown has gene- and stimulus-specific effects on inflammatory gene expression. SON is required for accurate splicing and expression of GBF1, a key mediator ofcis-Golgi structure and function. Chemical GBF1 inhibition has similar effects toSONknockdown, suggesting that SON controls macrophage functions at least in part by controlling Golgi-associated processes.