Regulation of macrophage iron homeostasis is associated with the localization of bacteria

Abstract

Iron not only plays an important role in the physiological function of organisms but also is an essential nutrient for the growth of pathogens. There is a competing relationship between organisms and pathogens for the use of iron in the case of infection. The macrophage, as the first immune cell found to participate in iron metabolism, has a precise regulation system to maintain iron homeostasis in response to pathogen infection. However, few studies have compared the effects of different types of bacterial infections on the iron homeostasis of macrophages. In this study, we investigated the changes in the iron regulation of the macrophage 3D4/2 by the infection of the extracellular bacterium Escherichia coli K88 (E. coli K88) and the intracellular bacterium Salmonella typhimurium (S. typhimurium). We found that S. typhimurium infection reduced the uptake of extracellular iron, promoted the outflow transport of intracellular iron, and decreased the free iron ions for intracellular bacterial proliferation and utilization. However, the infection of E. coli K88 reversed iron regulation by promoting the uptake of extracellular iron, reducing the extracellular transport of intracellular iron and increasing the storage of iron in 3D4/2. The results demonstrated that macrophages had completely opposing regulations of iron metabolism in response to intracellular and extracellular bacteria. It suggested that the diversion of cellular iron traffic would be considered as an important defense mechanism for macrophages to reduce iron availability for bacteria, and the resistance of iron spread or the interruption of the assimilation of iron by bacteria would be beneficial in developing therapeutics for bacterial infection.