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Published on: April 29, 2015
Infection with Mycobacterium avium differentially regulates the expression of iron transport protein mRNA in murine
W Zhong1, W P Lafuse, B S Zwilling
1Department of Microbiology, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA.
Abstract:
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 free radicals via the Fenton/Haber-Weiss reactions. The iron transporter natural resistance-associated macrophage protein 1 (Nramp1) confers resistance to the growth of a variety of intracellular pathogens including Mycobacterium avium. Recently several other proteins that are involved in iron transport, including the highly homologous iron transporter Nramp2 and the transferrin receptor-associated protein HFE (hereditary hemochromatosis protein), have 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 proteins associated with iron transport in murine peritoneal macrophages. Both Nramp1 and Nramp2 mRNA levels increase following infection, while the expression 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 they may play an important role in host defense by maintaining a delicate balance between iron availability for host defense and at the same time limiting iron availability for microbial growth.
Insights
This study reveals how Mycobacterium avium infection alters iron transporter gene expression in macrophages. Nramp1 and Nramp2 mRNA levels rise, while transferrin receptor mRNA decreases, impacting host defense against pathogens.
Area of Science:
- Immunology
- Molecular Biology
- Microbiology
Background:
- Iron is crucial for microbial growth and host defense, catalyzing free radical generation.
- The natural resistance-associated macrophage protein 1 (Nramp1) is known to confer resistance to intracellular pathogens like Mycobacterium avium.
- Other iron transport proteins, including Nramp2 and HFE, have been identified, but their roles in host defense are unclear.
Purpose of the Study:
- To investigate the relationship between iron transport proteins and host defense against intracellular pathogens.
- To examine how Mycobacterium avium infection affects the expression of iron transport-related genes in macrophages.
Main Methods:
- Murine peritoneal macrophages were infected with Mycobacterium avium.
- Messenger RNA (mRNA) expression levels of Nramp1, Nramp2, transferrin receptor, and HFE were analyzed.
Main Results:
- Mycobacterium avium infection led to increased mRNA levels of both Nramp1 and Nramp2 in macrophages.
- Transferrin receptor mRNA expression decreased following infection.
- HFE mRNA expression remained unchanged.
Conclusions:
- Differential regulation of iron transport proteins suggests a role in host defense.
- These proteins may balance iron availability for host defense while limiting microbial access.
- Understanding these mechanisms is key to developing strategies against intracellular pathogens.
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