Activation of TLR9 in mouse macrophages that reside in fatty tissue is likely to release chemokines like CCL2 attracting immune cells and driving fatty tissue inflammation as seen in obesity.647 Similar disease-promoting effects have been described for TLR9-dependent proinflammatory cytokine release from liver resident macrophages and TLR9-driven release of IFN-α by pDCs in nonalcoholic steatohepatitis648,649 and type 1 diabetes,650 respectively. The gene discussed is TLR9; the disease is obesity due to melanocortin 4 receptor deficiency.