Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rare blood disease improves the defence against germs

16.02.2017

Researchers of the HZI and of the University of Magdeburg find increased immune reaction associated with a rare bone marrow disease

Patients afflicted by myeloproliferative neoplasia – a group of chronic malignant bone marrow diseases – bear a mutation in their haematopoietic stem cells. The mutation leads to the bone marrow producing too many blood cells, which thickens the blood.


Blood smear of a myeloproliferative neoplasia patient with a significant increase in the number of platelets (purple) as compared to the clearly larger red blood cells.

Ed Uthman/CC BY 2.0


Schematic model of a T cell.

Pixabay

This can lead to blood clots or clogged blood vessels, which may trigger, e.g., a stroke. Scientists of the Helmholtz Centre for Infection Research (HZI) in Braunschweig and of the Otto von Guericke University Magdeburg recently discovered that certain cells of the immune system also bear this mutation in those patients that possess a particularly large number of altered stem cells. The impact of this scenario on the defence against pathogens was investigated in mice by the scientists. They published their results in Leukemia.

The bone marrow harbours the haematopoietic stem cells that produce the various types of red and white blood cells and platelets. They are induced to do so by messenger substances that bind to them and trigger a reaction chain, in which many different components partake. In a rare malignant group of blood diseases called myeloproliferative neoplasia (MPN), most of the patients have haematopoietic stem cells that bear an error in their genetic material – a mutation.

The mutation usually resides in a certain component of the reaction chain called Janus kinase 2 and causes the signal for haematopoiesis to be permanently switched on in the stem cells. Depending on which type of stem cell is afflicted, the bone marrow of the patients produces the corresponding blood cells – the blood becomes too thick and may clog the vessels.

MPN patients usually are treated with an inhibitor of Janus kinase 2 that suppresses the continuous signal triggering haematopoiesis. However, this also weakens the immune cells such that the patients become more susceptible to infections.

Prof Dirk Schlüter of the Otto von Guericke University Magdeburg, who is associated with the Helmholtz Centre for Infection Research (HZI) in Braunschweig, investigated patients with different severities of myeloproliferative neoplasia in a close cooperation with the haematologists, Prof Florian Heidel and Prof Thomas Fischer from Magdeburg. They found that 60 per cent of the patients, who have a particularly large number of damaged stem cells, bear the mutation in their so-called T cells as well. These cells of the immune system specifically fight against pathogens that entered the body.

"It was previously unknown that so many MPN patients bear the mutation in their T cells as well," says Dirk Schlüter. "In order to find out what this actually means for the patients, we combined the clinical studies with studies on mice." For this purpose, the scientists in Schlüter's team bred mice, whose T cells bear the Janus kinase 2 mutation, and compared these animals to healthy mice.

"Despite the mutation, the mice seemed to be well-off, there was no difference to the control animals," Schlüter says. The scientists then infected the mice with Listeria monocytogenes. Listeria bacteria colonise food items and can cause severe infections in humans including meningitis. When the scientists investigated the mice, they found: Seven days after the infection with Listeria, the mice with the mutated T cells had 100-fold lower levels of bacteria in their spleen than the control mice.

They had formed clearly more specific T cells directed against Listeria and were thus able to control the infection better than the control animals without a mutation in T cells. "We also looked at the numbers of the other blood cells in the spleen of the infected animals: Not only the T cells, but also the granulocytes and the precursors of erythrocytes were strongly increased in the mice bearing the mutation," Schlüter says. "Again, this makes the blood too thick and there is a risk of thrombosis. In addition, inflammation parameters were elevated in the mice."

To exclude that the increased formation of blood cells was triggered by the Listeria bacteria alone, the scientists repeated the experiments with a plant lectin with a stimulatory effect on the immune system. "The lectin activated the immune system and the T cells of the mice – much like the Listeria bacteria," Schlüter says. "We observed the same effects as in the infection experiments: Mice bearing the T cell mutation showed a clearly stronger immune response, granulopoiesis and elevated haematopoiesis as well." This, he says, demonstrates that the vigorous reaction of the immune system truly is related to the mutation in the T cells.

As a next step, Dirk Schlüter and his team aim to look at the mechanism of T cell activation by the mutated Janus kinase 2 in order to find out why there is no counter regulation in the body. Moreover, it is not yet known what the mutation in the T cells means for patients afflicted by myeloproliferative neoplasia. "In collaboration with haematologists from the University Clinics in Magdeburg and Jena, we plan to find out if these patients might have more autoimmune symptoms, if they possibly have a different prognosis than other MPN patients and therefore might need a different therapy." Schlüter and Fischer are both members of the Health Campus Immunology, Infectiology and Inflammation (GC-I³) of the University of Magdeburg. True to the GC-I³s slogan „Understand Inflammation – Cure Diseases“, they are trying to understand inflammatory processes, which are the basis of so many common diseases, in order to prevent and cure those.

Original publication:
G. Nishanth, D. Wolleschak, C. Fahldieck, T. Fischer, A. Mullally, F. Perner, T.M. Schnöder, S. Just, F.H. Heidel and D. Schlüter: Gain of function in Jak2V617F-positive T-cells. Leukemia, 2017; doi: 10.1038/leu.2017.6

The press release and a picture are available on our website: https://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/rare_bloo...

The Helmholtz Centre for Infection Research (HZI):
Scientists at the Helmholtz Centre for Infection Research in Braunschweig, Germany, are engaged in the study of different mechanisms of infection and of the body’s response to infection. Helping to improve the scientific community’s understanding of a given bacterium’s or virus’ pathogenicity is key to developing effective new treatments and vaccines. http://www.helmholtz-hzi.de/en

Contact:
Susanne Thiele, Press Officer
susanne.thiele@helmholtz-hzi.de
Dr Andreas Fischer, Editor
andreas.fischer@helmholtz-hzi.de

Helmholtz Centre for Infection Research
Press and Communications
Inhoffenstr. 7
D-38124 Braunschweig
Germany

Phone: +49 531 6181-1404

Susanne Thiele | Helmholtz-Zentrum für Infektionsforschung

Further reports about: Infektionsforschung Listeria T cells bone marrow immune system stem cells

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

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...

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

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>