Infection with Mycobacterium avium differentially regulates the expressionof iron transport protein mRNA in murine peritoneal macrophages

Iron is an important element for the growth of microorganisms as well as in the defense of the host by serving as a catalyst for the generation of fre e radicals via the Fenton/Haber-Weiss reactions. The iron transporter natur al resistance-associated macrophage protein 1 (Nramp1) confers resistance t o the growth of a variety of intracellular pathogens including Mycobacteriu m avium. Recently several other proteins that are involved in iron transpor t, including the highly homologous iron transporter Nramp2 and the transfer rin receptor-associated protein HFE (hereditary hemochromatosis protein), h ave been described. The relationship of these proteins to host defense and to the growth of intracellular pathogens is not known. Here, we report that infection with M. avium differentially regulates mRNA expression of the pr oteins associated with iron transport in murine peritoneal macrophages. Bot h Nramp1 and Nramp2 mRNA levels increase following infection, while the exp ression of transferrin receptor mRNA decreases. The level of expression of HFE mRNA remains unchanged. The difference in the expression of the mRNA of these proteins following infection or cytokine stimulation suggests that t hey may play an important role in host defense by maintaining a delicate ba lance between iron availability for host defense and at the same time limit ing iron availability for microbial growth.