UW Health: UW researcher uncovers new type of immune response

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Madison, Wis. — Basic research in a University of Wisconsin laboratory has uncovered a new way that the human body fights off viral infections, opening the door to novel treatments for such diseases as hepatitis and yellow fever.

Dr. Michael Carrithers, associate professor of neurology, studies the concept of innate immunity, a type of immune defense that responds immediately to pathogens such as viruses.

In his latest study, he describes how a novel channel protein in human macrophages recognizes the molecular pattern of a pathogen, produces an electric current, and sends signals that turn on specific immune response genes. These genes, in turn, produce substances such as interferon beta to fight the infection. A macrophage is a type of white blood cell that engulfs and devours cellular waste, sort of like PacMan in the old video game. Channel proteins are responsible for electrical signaling in brain cells but have not been shown previously to activate an immune response.

The Carrithers team used a synthetic molecule that mimics viral RNA and discovered that it activated the channel current in the macrophage. This activation then turned on genes to initiate an immune response. Such a system could be stimulated by a vaccine or targeted to help fight off viral infection. This new class of pattern recognition receptors may be particularly important in fighting off infections in humans.

“What this means is that we now have a new approach to develop better vaccines and treatments against many types of viruses,” he says. “These viruses include common viruses such as influenza and herpes and other viruses that cause severe diseases throughout the world including yellow fever, dengue fever, hepatitis, and West Nile virus.”

The trick, he adds, will be stimulating such an immune response without triggering dangerous levels of inflammation. It has been difficult to target other pattern recognition receptors with drugs, but it is much easier to develop orally active medications to regulate channel proteins. In an earlier study, Carrithers designed a genetically modified macrophage that protected and helped heal neural cells in a mouse model of multiple sclerosis.

Other members of the Carrithers lab include Alexis Jones, Danielle Kainz, Faatima Khan, and Cara Lee. The study was published in the Journal of Biological Chemistry and is available online: http://www.jbc.org/content/early/2014/11/03/jbc.M114.611962