Unintended Consequences: Immune Response to Influenza May Trigger Life-Threatening Bacterial Infections

Providing insight into why the influenza virus can lead to dangerous bacterial infections such as bronchitis or pneumonia, a Yale School of Medicine study reveals that the flu causes a systemic suppression of the body’s innate immune response. While necessary to prevent an excessive and perhaps lethal inflammatory response, the immune suppression reduces the body’s ability to fight off secondary bacterial infections. The paper is published in the February 18 issue of Cell Host and Microbe.

While many studies have focused on how our body’s immune system protects us from a single pathogen such as the flu virus, it was unclear how this response alters the body’s ability to respond to a second infectious agent, such as bacteria.

To study what happens in coinfection – simultaneous infection with multiple pathogens – the Yale researchers infected one group of mice first with the influenza virus, and several days later with bacteria. A second control group was infected just with bacteria.

The team found that the bacteria-fighting innate immune systems were more severely compromised in the mice that had been infected with the flu virus than those infected only by bacteria.

“The virulence of the flu had somehow weakened the body’s ability to fight off further infection. We know in humans that this kind of secondary bacterial infection is what most often can kill flu patients,” explains lead author Ruslan Medzhitov, Ph.D., professor of immunobiology and Howard Hughes Medical Institute Investigator. Medzhitov is also the winner of the 2010 Lewis R. Rosenstiel Award for Distinguished Work in Basic Medical Science.

Further research revealed the mechanism for this suppression of the immune system. The team found that lung damage from the viral infection had triggered a sustained increase in serum glucocorticoid levels. Glucocorticoids are produced by the adrenal glands during times of psychological and physiological stress and suppress the inflammatory and immune responses. This process is helpful, even life-saving in the case of influenza infection, because it prevents excessive inflammation that can be deadly. But the irony is that it also neutralizes the weaponry needed by the systemic immune system to fight off secondary bacterial infection.

Medzhitov explains, “By suppressing inflammation the body chooses to fight the greater of two evils, but this in turn creates a window of vulnerability to secondary infections.”

Other authors are Amanda M. Jamieson of the Howard Hughes Medical Institute and the Department of Microbiology, Immunobiology and Genetics, University of Vienna, and Shuang Yu and Charles H. Annicelli of the Howard Hughes Medical Institute and the Department of Immunobiology, Yale School of Medicine.

Funding was provided by the Ellison Foundation, the Howard Hughes Medical Institute and the National Institutes of Health.

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Helen Dodson: helen.dodson@yale.edu, 203-436-3984