Hepcidin and its Regulatory Pathways in Malaria and in Adaptive Immunity

Iron is crucial for health – we need it for our red blood cells and immune system to function. However, iron is equally vital for the organisms that infect us; iron availability to microbes can determine the outcome of infection. This has been known for decades, but recently a small peptide called hepcidin has been identified as the key regulator of human iron transport. Hepcidin is at least as important for iron as insulin is for glucose. We are studying how hepcidin behaves in various infections including malaria, tuberculosis and HIV-1, how hepcidin and the immune system interact, and testing whether new therapies can be based around measurement and manipulation of hepcidin. Most infections increase hepcidin levels, but hepatitis C virus instead lowers hepcidin. We found HCV deactivates the cellular components that normally stimulate synthesis of hepcidin. We hypothesized that this behaviour might be advantageous for HCV if these hepcidin stimulators influenced replication of the virus. This seems to be the case, as we found that boosting the activity of the hepcidin stimulators prevented growth of HCV, due to unexpected antiviral properties that resemble the well-known functions of interferon. Understanding and exploiting this antiviral mechanism may lead to new types of antiviral therapy.