Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immunology Research Sheds New Light on Cell Function, Response

18.01.2013
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.

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."

According to Hardwidge, once bacteria such as C. rodentium and E. coli enter the body, the pathogens use a needle-like secretion apparatus to inject bacterial proteins into intestinal cells. Some of these proteins prevent the innate immune system from fighting the bacterium. One of these injected proteins is NleB.

Hardwidge and colleagues observed that the NleB protein binds with a protein in human cells named GAPDH. NleB modifies the GAPDH protein with a specific sugar molecule and prevents it from participating in a complex biochemical pathway that ultimately allows the innate immune system to respond efficiently to pathogens.

"The function of GAPDH in this pathway was less clear before we did these experiments," Hardwidge said. "GAPDH has well-known functions in the metabolism, but we observed that it also participates in how a cell responds to an infecting bacterium. We're very interested in the fact that this metabolic enzyme has apparently evolved also to be an important part of the innate immune system."

Hardwidge said that E. coli and C. rodentium using the NleB protein to target GAPDH and inhibit innate immunity is also an interesting finding, which will be characterized in greater detail in continuing studies.

With a more advanced understanding about how the innate immune system responds biochemically to invading bacteria -- and how those bacteria suppress the response -- scientists may be able to advance research and therapeutic drug development in other diseases, Hardwidge said. For example, cancers, Crohn's disease and Rheumatoid arthritis all are tied to overactive inflammation. In some cases, the same pathway in which GAPDH participates regulates the inflammation.

"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. "We have a general understanding about this important pathway that triggers a defensive response. But when you get into the details of how this pathway is regulated, we're still learning and understanding what exactly is going on. Now, low and behold, there is a new protein involved."

Philip Hardwidge | Newswise
Further information:
http://www.k-state.edu

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>