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 New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>