Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Single protein is key in response to bacterial, viral infections

21.07.2003


A single protein acts as a key switch point in frontline immune system reactions to both bacterial and viral infections, according to a report published online today in the journal Nature. In determining how this protein functions, a team of scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID) can now explain why certain symptoms, such as fever, occur regardless of the cause of infection.



Bruce Beutler, M.D., of The Scripps Research Institute in La Jolla, CA, who led the team, says, "This protein, Trif, stands at a crossroads in the mouse innate immune system and, by inference, we believe in the human immune system as well." A clear understanding of Trif’s role in sparking inflammation gives scientists an obvious target for drugs designed to combat the runaway inflammation characteristic of many infectious and immune-mediated diseases.

Mammals, including humans, employ a family of proteins (called toll-like receptors, or TLRs) in first-line defense against bacteria and viruses. One protein, TLR-3, is activated by viruses, while another, TLR-4, responds to molecules frequently contained in bacterial cell walls. The TLRs are an important part of the innate immune system, the all-purpose "first-responder" arm of the immune system. Once activated by invading pathogens, TLRs relay the alarm to other actors in the immune system. In short order, the innate immune system responds with a surge of chemicals that together cause inflammation, fever and other responses to infection or injury.


Defining the intervening steps in the signaling pathway from TLR activation to inflammatory response is an important objective of Dr. Beutler’s research. Previously, scientists had discovered a "transducer" protein responsible for passing on the news of a bacterial attack. Mice lacking this protein could still fight bacterial infection, although not very well. There had to be at least one more transducer protein.

Dr. Beutler’s team found this mystery protein through a technique called forward genetics. Genetic mutations are randomly introduced into strains of mice. A sensitive screening mechanism allows the researchers to pick out any mice that, by chance, show interesting characteristics, such as weakened responses to infection. In the latest research, Dr. Beutler and his colleagues identified a mouse whose immune system did not react to a substance called endotoxin, a component of bacterial cell walls. Subsequently, the team determined the consequence of the genetic error in these mice -- they cannot produce working Trif protein.

Lack of Trif explained why the mutant mice could not respond adequately to endotoxin (which mimics bacterial infection). However, Dr. Beutler notes, the team also made the surprising observation that mice missing Trif are also unable to respond to the double-stranded RNA produced by most viruses and thus could not fight off viral infections.

The scientists inferred that both the bacteria-sensing TLR-4 pathway and the virus-sensing TLR-3 pathway are blocked when Trif is defective. This is the first innate immune system transducer protein discovered that mediates signals generated by both bacterial and viral infection.

"Scientists have been searching for the endotoxin signaling molecules of the innate immune system for more than four decades," says Daniel Rotrosen, M.D., director of NIAID’s Division of Allergy, Immunology and Transplantation. "We’ve witnessed an explosion of information on innate immunity in the past five years, catalyzed by the discovery of the TLR family of signaling molecules," he adds. "NIAID’s grant to Scripps enables scientists from diverse disciplines spanning biology and informatics to tackle a wide variety of problems in innate immunity. This finding is the first of what we anticipate will be many discoveries made possible by forward genetics and other cutting-edge technologies supported through this grant."

Anne A. Oplinger | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

Quantum optical sensor for the first time tested in space – with a laser system from Berlin

23.01.2017 | Physics and Astronomy

The interactome of infected neural cells reveals new therapeutic targets for Zika

23.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>