Mechanism of impaired iron release by the reticuloendothelial system during the hypoferremic phase of experimental Neisseria meningitidis infection in mice

Abstract

Hypoferremia, the reduction of plasma transferrin iron levels during infection, has been shown to control Neisseria meningitidis infection in mice. The exact nature of the mechanism that regulates this response has been obscure. We have previously shown that hypoferremia does not result from an accelerated removal of iron from the plasma transferrin pool. In this study, we have examined the processing of iron by the reticuloendothelial system during infection. Normal and hypoferremic meningococcus-infected mice were injected with 59Fe-labeled erythrocytes. Kinetics of uptake and redistribution of the label indicated that during the hypoferremic phase of the infection, reticuloendothelial system-processed iron was not returned to the plasma transferrin pool. Fractionation of hepatic cellular compartments showed that this impaired release of iron resulted from a preferential incorporation of heme-derived iron into the intracellular ferritin pool during the hypoferremic phase of the infection. These findings indicate that this withholding of iron within the intracellular pool leads to hypoferremia and therefore denies the extracellular pathogen its essential iron.