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Celebrating Five Years of the Doherty Institute


Understanding immune response to secondary infections

The World Health Organization estimates that between 290,000 to 650,000 die following complications from influenza each year, but it’s not the virus itself that causes these fatalities.

“Flu deaths are commonly caused by lower respiratory tract infections and pneumonia - a leading cause of death from infectious disease,” explains University of Melbourne Professor Jose Villadangos, who has a joint appointment at the Doherty Institute and the Bio21 Institute.

“After an initial severe infection, patients may be at high risk of contracting secondary infections and developing fatal pneumonia.”

Professor Villadangos and his team discovered this is due to the immune system being left paralysed by the initial infection.

“Recovery from the viral infection leaves an ‘immunological scar’ that reduces the immune system’s capacity to launch protective responses against subsequent infections,” he says.

“We are not evolved to survive the level of inflammatory assault that would send a person to the intensive care unit. Modern medicine is the only reason we survive.

“But this comes at a cost: the same processes that are normally at work to stop inflammation after the resolution of infection, ‘overshoot’ in survivors from severe illness, leaving them immunosuppressed, a phenomenon we have termed ‘immunological paralysis’.”

To uncover the mechanism for the immunosuppression, using tests in mice and observations in humans, the researchers measured the levels and activity of immune cells responsible for fighting infection. They also looked at the levels of certain messenger molecules, called cytokines, and other factors that activate or suppress the immune system.

“Following a primary infection, the immune system essentially undergoes a reprogramming that can persist for weeks and cause immunosuppression, increasing susceptibility to further infections,” says Professor Villadangos.

“Our current focus is on dampening the immune system. While this is necessary to prevent organ damage by excessive inflammation, we also need to avoid establishing an ‘immunological scar’ that leaves patients susceptible to secondary pneumonia,” says Professor Villadangos.

Instead, the immune system can be supported to better fight secondary infections.

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