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.