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 Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>