Scientists at Cancer Research UK's London Research Institute (now part of the Francis Crick Institute) have uncovered one mechanism that underlies natural immunity to fungal infections in the blood, or sepsis.
The research has implications for therapies to boost immunity to fungal sepsis in people who are at risk, such as cancer patients with compromised immune systems due to treatment.
Dr Caetano Reis e Sousa of LRI explained: "Fungal organisms such as Candida albicans inhabit our body surfaces but are usually largely harmless due to the barriers provided by our skin and by the action of our immune systems.
"However if our immunity is compromised or if our skin is broken (for example by wounds), the fungus can invade underlying tissues and cause disease. In fact, in some cancer patients where immunity is sometimes compromised, blood spread of Candida can be a serious concern.
"Similarly, spread of Candida through the blood (known as Candida sepsis) can occur in patients who have a cannula inserted into their body or who undergo deep tissue surgery."
Until now, it was unclear how the body defends itself against Candida sepsis - although it was known that a type of disease-fighting white blood cells known as neutrophils are key to gobbling up and killing fungal organisms that get trapped in the kidneys after entering the blood.
To investigate further, the researchers studied a mouse model of systemic fungal infection with Candida albicans. They found that this killing function of neutrophils in the kidneys is regulated by another type of white blood cells, known as natural killer (NK) cells who, in turn, get their instructions from dendritic cells - yet another type of white blood cells.
Dendritic cells are well known for detecting pathogens and initiating immunity to infection - although this unusual relay from dendritic cells to NK cells to neutrophils has not previously been described.
Notably, the researchers found that dendritic cells use a special pathway to detect the fungus, known as the Syk pathway. In fact, if the protein called Syk is taken out of dendritic cells, the whole system crashes - NK cells do not get their instructions and cannot help neutrophils kill the fungus, which grows out of control.
Dr Reis e Sousa added: "By unravelling this pathway of anti-fungal immunity, we have uncovered a crucial function of Syk in dendritic cells that suggests it might be a useful target for treatments to boost resistance to fungal sepsis in at-risk patient groups."
The paper, Syk Signaling in Dendritic Cells Orchestrates Innate Resistance to Systemic Fungal Infection, is published in PLOS Pathogens.
