Type 1 interferons, a family of proteins that trigger the body's
immune responses to many pathogens, can drive inflammation, lung
damage and even death in influenza infection, according to new
research from the Medical Research Council's National Institute for
Medical Research (NIMR; now part of the Francis Crick
Institute).
Dr Andreas Wack of NIMR explained: "The severity of disease
caused by influenza varies hugely - ranging from mild symptoms to
death. What determines the severity is unclear, but the ability of
different virus strains to cause disease and the age or immune
status of infected individuals are all thought to play a part.
"The role of genetically-determined factors in infected people
is less well understood. Clusters of severe flu within families
suggest that some people are more susceptible than others. Studies
in mice show a wide range of genetic susceptibility - and many
genes have been proposed to contribute to susceptibility or
resistance."
Type 1 interferons are widely recognised as having an antiviral
function in many virus infections, and are known to block influenza
virus replication in the laboratory. However, it is less clear what
the effect of interferons are in an influenza-infected organism in
real life.
Dr Wack's team at NIMR studied mice of different genetic
backgrounds to show a direct correlation between high rates of
illness and death and high levels of type 1 interferon in response
to influenza infection. While a moderate type 1 interferon response
contributes to protection during influenza infection, strains of
mice with a genetic propensity for a high type 1 interferon
response experienced high levels of inflammatory molecules and
cells, leading to severe lung damage.
In these susceptible mice with high type 1 interferons, stopping
type 1 interferon signalling or removing the cells which produce
them reduced influenza induced illness and death.
Dr Wack said: "When virologists think of interferons, they think
of antiviral effects, and this is how they were discovered. We were
therefore very surprised when we found that high levels of type 1
interferon do not protect but have a disease-causing effect in
influenza infection. Under these circumstances, the inflammatory
effect of type I interferons overrides their antiviral function,
causing more harm than good."
PhD student Sophia Davidson of NIMR added: "We think our
observations have important implications for predicting
susceptibility to severe flu in humans and for treating the disease
caused by this infection.
"Some people may have high numbers of the cells that produce
type 1 interferon or a predisposition to strong interferon
responses, and this may be a risk factor for severe influenza. We
are now trying to understand whether this is in fact the case."
The paper, Pathogenic potential of interferon ?? in acute influenza
infection, is published in Nature
Communications.