Immune system has a back up plan

December 22, 2010

New research by scientists at the University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences reveals that the immune system has an effective backup plan to protect the body from infection when the "master regulator" of the body's innate immune system fails. The study appears in the December 19 online issue of the journal Nature Immunology

The innate immune system defends the body against infections caused by bacteria and viruses, but also causes inflammation which, when uncontrolled, can contribute to chronic illnesses such as heart disease, arthritis, type 2 diabetes and cancer. A molecule known as nuclear factor kappa B (NF-κB) has been regarded as the "master regulator" of the body's innate immune response, receiving signals of injury or infection and activating genes for microbial killing and inflammation.

Led by Michael Karin, PhD, Distinguished Professor of Pharmacology, the UC San Diego team studied the immune function of laboratory mice in which genetic tools were used to block the pathway for NF-κB activation. While prevailing logic suggested these mice should be highly susceptible to bacterial infection, the researchers made the unexpected and counterintuitive discovery that NF-κB-deficient mice were able to clear bacteria that cause a skin infection even more quickly than normal mice.

"We discovered that loss of NF-κB caused mice to produce a potent immune-activating molecule known as interleukin-1 beta (IL-1β), which in turn stimulated their bone marrow to produce dramatically increased numbers of white blood cells known as neutrophils," said Karin. Neutrophils are the body's front-line defenders against infection, capable of swallowing and killing bacteria with a variety of natural antibiotic enzymes and proteases.

The new research demonstrates that the innate immune system deploys two effective strategies to deal with invasive bacterial infection, and that the IL-1β system provides an important safety net when NF-κB falls short.

"Having a backup system in place is critical given the diverse strategies that bacterial pathogens have evolved to avoid bacterial clearance," said Victor Nizet, MD, professor of pediatrics and pharmacy, whose laboratory conducted the infectious challenge experiments in the study. "A number of bacteria are known to suppress pathways required for NF-κB activation, so IL-1β signaling could help us recognize and respond to these threats."

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