Scientists have discovered a way to stop a deadly fungal infection from hijacking the body's immune system and spreading to the brain. Researchers, including those from Universities of Sheffield in the UK and Harvard Medical School in the US, studied Cryptococcosis, a disease that infects humans and animals after breathing in airborne fungi.
The disease can result in a lung infection that may subsequently spread to the brain by hitching a lift inside the white blood cells. Researchers identified signals that white blood cells use to control their behaviour and found that a molecule called ERK5 could be manipulated to encourage white blood cells to throw out the pathogens. "When an infection starts, the first white blood cell to respond is called a macrophage," said Robin May, from University of Birmingham in the UK.
"This identifies the invading bacteria or fungus, destroys it and then alerts the rest of the immune system," said May. "However, in the case of some diseases like Cryptococcosis, the invading organism has evolved to be able to survive inside that white blood cell and then use them like a transport system to help move around the body," he said. Many white blood cells overcome this by throwing those hijackers out, using a mechanism called vomocytosis.
However, researchers do not know how vomocytosis is controlled. There are many diseases apart from Cryptococcosis in which pathogens - bacteria, viruses, fungi or parasites that can cause disease - survive by hijacking the immune system. Researchers wanted to identify the mechanism that allows white blood cells to recognise and expel these hijackers. "If we can develop ways to manipulate this and encourage the white blood cells to recognise and expel organisms like this, we might be able to limit the spread of infection not only for Cryptococcosis but for other invasive pathogens that are a significant threat to human health worldwide," researchers said.
They identified signals that white blood cells use to control their behaviour and disabled those signals one by one. In the process, the researchers discovered that a molecule called ERK5 could be manipulated to encourage white blood cells either to throw out pathogens better or to keep them inside and try to kill them for longer.
"We found that by blocking ERK5 in zebrafish, we were able to increase vomocytosis rates in their white blood cells and so prevent a deadly fungal infection from spreading to the brain," said May. "Our hope is that we will be able to develop therapies that target this process, such as drugs that would be able to limit an infection and prevent it from spreading from the initial site of attack," he said. The findings were published in the journal Science Advances.