Dopamine alters macrophage metabolism promoting intracellular Mycobacterium tuberculosis survival

Abstract

Dopamine (DA) is thought to aggravate progress of bacterial infections and enhance risk of intracellular bacterial infection like tuberculosis (TB). Though TB patients are known to present with high dopamine levels the causal link between them has remained unexplored. Mycobacterium tuberculosis (M. tb) , the causative agent of TB, requires a copious supply of iron and carbon for survival and proliferation within host cells. In vitro and i n vivo administration of dopamine induced an increase of non-transferrin bound iron delivery into macrophages along with and lipid accumulation and foamy macrophage formation. The resultant intracellular milieu provided an abundant source of carbon and iron for invading M. tb pathogen. Binding of dopamine to iron was characterized by NMR spectroscopy implicating its role in intracellular trafficking. Using iron sensor M. tb strain, we observed elevated iron levels in intraphagosomal bacteria residing in dopamine treated cells while CFU analysis indicated enhanced M. tb survival and proliferation. We found that DA modulates macrophage metabolism resulting in creation of iron and lipid nutrient rich intracellular micro-environment favorable for survival of M. tb . Survival of M. tb bacilli in dopamine treated macrophages was significantly enhanced demonstrating that dopamine leads to creation of an intracellular milieu that provides a conducive and nurturing environment for invading pathogenic bacilli.