Uncovering the divergent roles of type I and III Interferons in Salmonella infection

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Researchers discovered more than 60 years ago that cells infected with viruses produce a substance that protects neighbouring cells from viral infection. This secreted substance was termed Interferon, as it 'interferes' with infection. Since then, many different interferons have been discovered, and their functions in anti-viral immunity have been extensively studied. Interferons has even been used as a therapy against viral infections. However, it remains unclear whether interferons have similar roles during bacterial infections. Bacterial infections pose a significant threat to human health and there are increasing numbers of bacteria that are resistant to almost all clinically available antibiotics. It is therefore essential that we discover alternative treatments for bacterial infections. An attractive area of research are drugs that activate the immune system to naturally combat infection. Interferons are one such candidate anti-bacterial therapy, but we first need a greater understanding of their roles in bacterial infection, in part to see if they could have harmful effects.This proposal will focus on the major human pathogen Salmonella enterica, a bacterium which affects over 100 million people each year, causing different diseases including gastroenteritis and typhoid fever. Salmonella invades human cells where they multiply and hide from the immune system. Worryingly, resistant strains of Salmonella are emerging across the globe, rendering this pathogen a major threat to human health. In this proposal, we will study whether different interferon families play beneficial or harmful roles in Salmonella infection. We will investigate how interferons affect the ability of Salmonella to multiply within host cells and control immune responses. We will also study the functions of different interferons in mice infected with Salmonella. This project will also identify if virulence proteins that Salmonella uses to cause disease can alter the ability of cells to produce or respond to interferon.Overall, this research will give us a better understanding of the functions of interferons in Salmonella infection, and how we can use this knowledge to develop new treatments for Salmonella infections.