K-State Leads Study That Makes Immune System Breakthrough

Relationship between protein and innate immune system determines response to pathogens

Published on: Jan 22, 2013

A Kansas State University-led study has uncovered new information that helps scientists better understand the complex workings of cells in the innate immune system. The findings may also lead to new avenues in disease control and prevention.

Philip Hardwidge, associate professor of diagnostic medicine and pathobiology, was the study's principal investigator. He and colleagues looked at the relationship between a bacterial protein and the innate immune system -- a system of defensive cells that responds rapidly to an infection in a nonspecific manner.

Among their findings, the researchers characterized a new protein that affects how cells in the innate immune system function and protect humans against invading bacteria such as E. coli O157:H7. The study, "NleB, a Bacterial Effector with Glycosyltransferase Activity, Targets GAPDH Function to Inhibit NF-kappaB Activation," was published in the most recent issue of the scientific journal Cell Host and Microbe. The National Institutes of Health's National Institute of Allergy and Infectious Diseases funded the study.

"The cell is so complicated, its amazing that it even works at all, especially when you consider that it is three-dimensional and compartmentalized," Hardwidge said
"The cell is so complicated, it's amazing that it even works at all, especially when you consider that it is three-dimensional and compartmentalized," Hardwidge said

Hardwidge conducted the study with lead author Xiaofei Gao, a doctoral student at the University of Kansas Medical Center and now employed as a postdoctoral fellow at the Whitehead Institute; and with Thanh Pham and Leigh Ann Feuerbacher, postdoctoral research fellows in diagnostic medicine and pathobiology at Kansas State University. Colleagues at the University of Kansas Medical Center; the Institute of Infectiology in Muenster, Germany; and the Stowers Institute for Medical Research also contributed to the study.

The research team studied a bacterium that infects mice, named Citrobacter rodentium. The bacterium is similar to E. coli O157:H7, which causes diarrheal illness in humans. Both bacteria use the protein NleB to inhibit the innate immune system from fighting the bacteria.

"NleB is very important to the ability to cause disease," Hardwidge said. "Epidemiological and functional studies on E. coli and C. rodentium have shown that the presence of the NleB protein is associated with the ability of E. coli and C. rodentium to cause severe disease in humans and mice, respectively. But how the NleB protein did this was unknown."

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