Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sensor of bacteria and viruses on high alert at the site of action

15.01.2013
Researchers show: Sophisticated transport system helps immune cells quickly detect infections

"Danger!" signals TLR9, the molecular sensor, whenever it recognizes bacterial or viral genetic information, specifically DNA. Instantly, the immune system initiates the process of fighting off the infection.


This immune cell produces TLR9, which glows green when irradiated with laser light. The molecule is localized on the edge of tiny spheres within the cell, where it will ultimately encounter pathogenic DNA.

HZI/Oelkers

This initial protective mechanism is very fast because it focuses on recognition of basic structural properties – in this case bacterial or viral DNA. Now, researchers at the Helmholtz Centre for Infection Research (HZI) have shown that TLR9 not only quickly recognizes DNA, it also waits, ready for action, right at the site where it will encounter it.

It is through mechanisms like these that we gain valuable time before acquired immunity, the more effective but much slower branch of the immune system, is activated. Together with their German, US, and South Korean colleagues, HZI scientists have examined what the requirements for TLR9 function are in different kinds of immune cells. The researchers have now published their findings in “The Journal of Immunology”, which has ranked this research among the top ten percent of the scientific journal's total published contributions.

The scientists expect that their insights might be exploited for therapeutic purposes. "In addition to its classic job, TLR9 could potentially help with disease prevention. One option, which is currently under investigation in clinical studies, is adding DNA to vaccines - to switch on TLR9 and thereby activate the immune system more strongly," explains Prof. Melanie Brinkmann, head of HZI's Viral Immune Modulation research group. In other instances it may make sense to inhibit this molecule - as in those cases where it erroneously recognizes the body's own DNA, causing autoimmune diseases. "In order to fully grasp the potential of this and similar molecules, we need to better understand how TLR9 functions in immune cells," explains Brinkmann. The researchers are especially interested in figuring out how the molecule gets from the location within the cell where it is produced into the endolysosomes. It is inside these tiny bubbles that it ultimately encounters the DNA of invading bacteria or viruses.

To trace TLR9's movements within the cell, the researchers developed a murine model, in which mice produced a color-labeled version of the protein. With the help of a microscope, the scientists were able to localize TLR9 inside different immune cells, revealing how it is capable of such a rapid response. Prior to a bacterial or viral infection, the sensor migrates into the endolysosomes to "await" potential intruders. By thus positioning TLR9, the cell ensures a given pathogens' rapid detection.

In order to be fully operational, a portion of the protein must first be cleaved off – this is done by “molecular scissors”, which the researchers identified as well. Both transport into the endolysosomes and cleavage of the protein depend upon the presence of a second protein called UNC93B1. "We thus managed to identify a number of important components that are key to TLR9's ability to recognize bacterial and viral intruders and set off an alarm," says Dr. Margit Oelkers, another HZI scientist involved in the project. Studying TLR9's transport within different immune cell types, the researchers found out that the process actually varies from one cell type to the next. Says Brinkmann: "The results are helping us better understand how TLR9 works. Our findings are critical if we are to exploit the molecule's properties for therapeutic purposes."

Original publication
Ana M. Avalos, Oktay Kirak, J. Margit Oelkers, Marina C. Pils, You-Me Kim, Matthias Ottinger, Rudolf Jaenisch, Hidde L. Ploegh und Melanie M. Brinkmann
Cell-Specific TLR9 Trafficking in Primary APCs of Transgenic TLR9-GFP Mice
The Journal of Immunology 2013 190:695-702

Ideally, our immune system will recognize and subsequently eliminate pathogens that enter our bodies. However, many microorganisms and viruses have evolved strategies to evade immune detection. The “Viral Immune Modulation” research group seeks to uncover the different mechanisms that particularly herpes viruses use to perform this feat.

The Helmholtz Centre for Infection Research (HZI):
The Helmholtz Centre for Infection Research contributes to the achievement of the goals of the Helmholtz Association of German Research Centres and to the successful implementation of the research strategy of the German Federal Government. The goal is to meet the challenges in infection research and make a contribution to public health with new strategies for the prevention and therapy of infectious diseases.

http://www.helmholtz-hzi.de/en

Dr. Birgit Manno | Helmholtz-Zentrum
Further information:
http://www.helmholtz-hzi.de/en
http://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/sensor_of_bacteria_and_viruses_on_high_alert_at_the_site_of_actio

More articles from Life Sciences:

nachricht Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

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 Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>