Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New weapon of the immune system discovered

14.08.2014

Aryl hydrocarbon receptor binds bacterial toxins and initiates their destruction

Max Planck researchers have discovered a completely new way in which the immune system recognizes pathogens. The aryl hydrocarbon receptor has long been a focus of research for pharma-cologists and toxicologists, as it recognizes environmental toxins.


Contact between tuberculosis pathogen and phagocyte (macrophage). The close contact between the pathogen and defense cell enables pigments such as phthiocol to enter the host cell. The recognition by the aryl hydrocarbon receptor leads to the rapid mobilization of defensive measures.

© MPI for Infection Biology / Volker Brinkmann

However, it also plays an important role in the immune system. A team of scientists headed by Stefan H. E. Kaufmann at the Max Planck Institute for Infection Biology in Berlin has discovered that virulence factors of bacteria which have invaded the body also bind to the aryl hydrocarbon receptor.

As a result, the innate immune response is activated and the factors are immediately broken down. With this finding, the scientists have identified a hitherto unknown component of the immune system: bacterial virulence factors can not only be neutralised by antibodies, but also directly destroyed.

Until now, immune biologists have largely ignored the possibility that the immune system directly destroys bacterial virulence factors. The role of the aryl hydrocarbon receptor, which is expressed in many cells including  immune and epithelial cells, is therefore all the more surprising.

Thus far the receptor was primarily known as a binding site for environmental toxins, among them the extremely harmful TCDD - a dioxin that causes devastating organ damage even in minute concentrations. “However, it occurs in a wide range of organisms from threadworms to insects through to humans. If it is found in so many living organisms, the reason is certainly not just to recognize environmental toxins, but also to defend against infections,” says Pedro Moura-Alves from the Max Planck Institute for Infection Biology.

The researchers therefore set out to identify bacterial molecules with a similar structure as the known binding partners of the aryl hydrocarbon receptor. They found what they were looking for in the form of bacterial pigments that are supposed to protect the pathogens but damage the body.

Mathematical models have shown that both the green-blue phenazines of the bacterium Pseudomonas aeruginosa, which causes nosocomial respiratory infections, and the yellow naphthoquinone phthiocol of the causative agent of tuberculosis Mycobacterium tuberculosis fit in the binding pocket of the receptor.

Experiments in mice then confirmed how important the aryl hydrocarbon receptor is for the immune response. Following infection with the lung pathogens, animals without these receptors develop more severe symptoms, have more bacteria in their lungs and are more likely to die. Evidently, the immune system does not recognize the foe early enough without the aryl hydrocarbon receptor.

“For the pathogen, the bacterial virulence factors are a blessing and a curse at the same time: on the one hand, they facilitate infection of the host organism, but on the other hand, they help the host to track down the microbe,” says Kaufmann.

What is special about the aryl hydrocarbon receptor is that it binds directly the bacterial pigments and then triggers the expression of several genes in the cell nucleus responsible for breaking down the virulence factors. To this end, it migrates from the outside into the interior of the nucleus where it binds to DNA.

The aryl hydrocarbon receptor is therefore a receptor and a transcription factor rolled into one and hence can react promptly to infection. By contrast, other receptors of the immune system have to rely on auxiliary proteins that relay the information about pathogens into the nucleus.

As a next step, the researchers want to find out what other transcription factors the aryl hydrocarbon receptor interacts with and what specific enzymes are responsible for breaking down the bacterial virulence factors.

Contact 

Prof. Dr. Dr. h. c. Stefan H.E. Kaufmann

Max Planck Institute for Infection Biology, Berlin

Phone: +49 30 28460-500
Fax: +49 30 28460-501

 

Dr. Sabine Englich

Max Planck Institute for Infection Biology, Berlin

Phone: +49 30 28460-142

 

Original publication

 
Pedro Moura-Alves, Kellen Faé, Erica Houthuys, Anca Dorhoi, Annika Kreuchwig, Jens Furkert, Nicola Barison, Anne Diehl, Antje Munder, Patricia Constant, Tatsiana Skrahina, Ute Guhlich-Bornhof, Marion Klemm, Anne-Britta Koehler, Silke Bandermann, Christian Goosmann, Hans-Joachim Mollenkopf, Robert Hurwitz, Volker Brinkmann, Simon Fillatreau, Mamadou Daffe, Burkhard Tümmler, Michael Kolbe, Hartmut Oschkinat, Gerd Krause, Stefan H.E. Kaufmann
AhR sensing of bacterial pigments orchestrates antibacterial defense
Nature, 13 August 2014, Advance Online Publication (AOP), doi: 10.1038/nature13684

Prof. Dr. Dr. h. c. Stefan H.E. Kaufmann | Max-Planck-Institute
Further information:
http://www.mpg.de/8356852/AhR-weapon-immune-system

Further reports about: Biology Infection damage pathogens receptor responsible toxins transcription

More articles from Life Sciences:

nachricht New Model of T Cell Activation
27.05.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Fungi – a promising source of chemical diversity
27.05.2016 | Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (HKI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Worldwide Success of Tyrolean Wastewater Treatment Technology

A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.

The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...

Im Focus: Computational high-throughput screening finds hard magnets containing less rare earth elements

Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.

The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...

Im Focus: Atomic precision: technologies for the next-but-one generation of microchips

In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.

In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...

Im Focus: Researchers demonstrate size quantization of Dirac fermions in graphene

Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices

Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.

Im Focus: Graphene: A quantum of current

When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene

In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

International expert meeting “Health Business Connect” in France

19.05.2016 | Event News

 
Latest News

11 million Euros for research into magnetic field sensors for medical diagnostics

27.05.2016 | Awards Funding

Fungi – a promising source of chemical diversity

27.05.2016 | Life Sciences

New Model of T Cell Activation

27.05.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>