Tumour necrosis factor (TNF), a messenger substance in the immune system, plays an important role in triggering chronic inflammatory diseases. For this reason, TNF inhibitors are a standard form of treatment for patients with rheumatoid arthritis and certain inflammatory bowel diseases. However, TNF also protects against infection, which means that inhibiting it can cause latent infections to resurface. Researchers have been investigating how TNF protects against infection for many years. In collaboration with researchers from Erlangen and beyond, a working group at FAU has now discovered a new mechanism via which TNF protects against intracellular pathogens that cause infection.
In order to defend the body against intracellular pathogens, such as the single-cell parasites Leishmania major, nitric oxide (NO) must be produced. This is formed in macrophages and other phagocytes through type 2 NO synthase (NOS2).
Macrophages (blue nucleus) that are infected with Leishmania major (purple) and have been stimulated with the messenger substance interleukin 4 produce arginase 1 (green).
Katrin Paduch/FAU Institute of Microbiology
When TNF is present arginase 1 expression is reduced considerably.
Katrin Paduch/FAU Institute of Microbiology
However, the function of NOS2 is inhibited by a competing enzyme called arginase 1. The researchers, led by PD Dr. Ulrike Schleicher and Prof. Dr. Christian Bogdan at FAU’s Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene, demonstrated through cell culture experiments and an infection model that tumour necrosis factor inhibits arginase 1 synthesis, which depends on the messenger substance interleukin 4. This causes nitric oxide production to increase and suppresses the pathogens.
‘As long as they can be confirmed in ongoing experiments with human cells, these findings provide a plausible explanation of the increased susceptibility to infection that occurs during anti-TNF treatments,’ explains Professor Bogdan, ‘In the future, concurrent use of arginase 1 inhibitors could minimise the risk of infection associated with TNF inhibition.’
The results of the study, which was partially carried out in the framework of FAU’s Interdisciplinary Centre for Clinical Research and DFG Collaborative Research Centre 1181, have recently been published in the international journal Cell Reports (DOI: 10.1016/j.celrep.2016.04.001)
Prof. Dr. Christian Bogdan
Phone: +49 9131 8522551
Dr. Susanne Langer | idw - Informationsdienst Wissenschaft
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
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,...
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...
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...
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...
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...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences